Rab5 is necessary for the biogenesis of the endolysosomal system in vivo
Abstract
An outstanding question is how cells control the number and size of membrane organelles. The small GTPase Rab5 has been proposed to be a master regulator of endosome biogenesis. Here, to test this hypothesis, we developed a mathematical model of endosome dependency on Rab5 and validated it by titrating down all three Rab5 isoforms in adult mouse liver using state-of-the-art RNA interference technology. Unexpectedly, the endocytic system was resilient to depletion of Rab5 and collapsed only when Rab5 decreased to a critical level. Loss of Rab5 below this threshold caused a marked reduction in the number of early endosomes, late endosomes and lysosomes, associated with a block of low-density lipoprotein endocytosis. Loss of endosomes caused failure to deliver apical proteins to the bile canaliculi, suggesting a requirement for polarized cargo sorting. Our results demonstrate for the first time, to our knowledge, the role of Rab5 as an endosome organizer in vivo and reveal the resilience mechanisms of the endocytic system.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Aβ catabolism genes RAB5A, RAB11A, CLU, and LRP2 are down-regulated in AD monocytes, suggesting impaired Aβ catabolism in AD monocytes.
“Similarly, several genes reported to be involved in Aβ catabolism, such as RAB5A, RAB11A, CLU, and LRP2 (49–53), were also down-regulated in AD monocytes, suggesting the impaired Aβ catabolism in AD monocytes.”
From Understanding monocyte-driven neuroinflammation in Alzheimer’s disease using human cortical organoid microphysiological systems (2025) · cites this paper as [49]
Cites
Rab proteins as membrane organizers
Zerial, M., & McBride, H. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35052055 · Cited by 3,381 · see citing works
Self-citationSNAREs — engines for membrane fusion
Jahn, R., & Scheller, R. H. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2002 · Cited by 2,635 · see citing works
The Mechanisms of Vesicle Budding and Fusion
Bonifacino, J. S., & Glick, B. S. (2004) · Cell · doi:10.1016/s0092-8674(03)01079-1 · Cited by 1,863 · see citing works
Rab Conversion as a Mechanism of Progression from Early to Late Endosomes
Rink, J. C., Ghigo, É., Kalaidzidis, Y. L., & Zerial, M. (2005) · Cell · doi:10.1016/j.cell.2005.06.043 · Cited by 1,680 · see citing works
Self-citationThe Liver: Biology and Pathobiology.
(1983) · Annals of Internal Medicine · doi:10.7326/0003-4819-98-5-690_3 · Cited by 1,615 · see citing works
ENDOCYTOSIS AND MOLECULAR SORTING
Mellman, I. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.575 · Cited by 1,521 · see citing works
The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway
Bucci, C., Parton, R. G., Mather, I. H., Stunnenberg, H. G., Simons, K., Hoflack, B., & Zerial, M. (1992) · Cell · doi:10.1016/0092-8674(92)90306-w · Cited by 1,370 · see citing works
Self-citationMukherjee, S., Ghosh, R. K., & Maxfield, F. R. (1997) · Physiological Reviews · doi:10.1152/physrev.1997.77.3.759 · Cited by 1,299 · see citing works
Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms
Akinc, A., Querbes, W., De, S., Qin, J., Frank-Kamenetsky, M., Jayaprakash, K. N., Jayaraman, M., Rajeev, K. G., Cantley, W. L., Dorkin, J. R., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.85 · Cited by 1,261 · see citing works
Self-citationA combinatorial library of lipid-like materials for delivery of RNAi therapeutics
Akinc, A., Zumbuehl, A., Goldberg, M. S., Leshchiner, E. S., Busini, V., Hossain, N., Bacallado, S., Nguyen, D. N., Fuller, J. E., Alvarez, R., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1402 · Cited by 1,228 · see citing works
Self-citationrab5 controls early endosome fusion in vitro
Gorvel, J., Chavrier, P., Zerial, M., & Gruenberg, J. E. (1991) · Cell · doi:10.1016/0092-8674(91)90316-q · Cited by 1,094 · see citing works
Self-citationLipid-like materials for low-dose, in vivo gene silencing
Love, K. T., Mahon, K. P., Levins, C. G., Whitehead, K. A., Querbes, W., Dorkin, J. R., Qin, J., Cantley, W., Qin, L. L., Racie, T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910603106 · Cited by 969 · see citing works
Self-citationThe Rab5 effector EEA1 is a core component of endosome docking
Christoforidis, S., McBride, H. M., Burgoyne, R. D., & Zerial, M. (1999) · Nature · doi:10.1038/17618 · Cited by 854 · see citing works
Self-citationIdentification of the Switch in Early-to-Late Endosome Transition
Poteryaev, D., Datta, S., Ackema, K., Zerial, M., & Spang, A. (2010) · Cell · doi:10.1016/j.cell.2010.03.011 · Cited by 752 · see citing works
Self-citationAdaptable adaptors for coated vesicles.
Robinson, M. (2004) · Trends in Cell Biology · doi:10.1016/j.tcb.2004.02.002 · Cited by 741 · see citing works
Mutations in human dynamin block an intermediate stage in coated vesicle formation
van der Bliek, A., Redelmeier, T., Damke, H., Tisdale, E. J., Meyerowitz, E. M., & Schmid, S. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.122.3.553 · Cited by 698 · see citing works
Membrane transport in the endocytic pathway
Gruenberg, J. E., & Maxfield, F. R. (1995) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(95)80013-1 · Cited by 645 · see citing works
Systems survey of endocytosis by multiparametric image analysis
Collinet, C., Stöter, M., Bradshaw, C. R., Samusik, N., Rink, J. C., Kenski, D. M., Habermann, B. H., Buchholz, F., Henschel, R., Mueller, M., et al. (2010) · Nature · doi:10.1038/nature08779 · Cited by 446 · see citing works
Self-citationVonderheit, A., & Helenius, A. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030233 · Cited by 437 · see citing works
Ang, A. L., Taguchi, T., Francis, S., Fölsch, H., Murrells, L. J., Pypaert, M., Warren, G., & Mellman, I. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200408165 · Cited by 432 · see citing works
Wucherpfennig, T., Wilsch‐Bräuninger, M., & González‐Gaitán, M. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211087 · Cited by 422 · see citing works
Damke, H., Baba, T., van der Bliek, A. M., & Schmid, S. L. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.131.1.69 · Cited by 410 · see citing works
GTPase activity of Rab5 acts as a timer for endocytic membrane fusion
Rybin, V., Ullrich, O., Rubino, M., Alexandrov, K. A., Simón, I., Seabra, M. C., Goody, R. S., & Zerial, M. (1996) · Nature · doi:10.1038/383266a0 · Cited by 326 · see citing works
Self-citationApical trafficking in epithelial cells: signals, clusters and motors
Weisz, O. A., & Rodriguez-Boulan, E. J. (2009) · Journal of Cell Science · doi:10.1242/jcs.032615 · Cited by 299 · see citing works
Reconstitution of Rab- and SNARE-dependent membrane fusion by synthetic endosomes
Ohya, T., Miączyńska, M., Coskun, Ü., Lommer, B. S., Runge, A., Drechsel, D. N., Kalaidzidis, Y. L., & Zerial, M. (2009) · Nature · doi:10.1038/nature08107 · Cited by 235 · see citing works
Self-citationUnsolved Mysteries in Membrane Traffic
Pfeffer, S. R. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.061705.130002 · Cited by 216 · see citing works
Kipp, H., Pichetshote, N., & Arias, I. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007794200 · Cited by 179 · see citing works
Futter, C. E., Connolly, C. N., Cutler, D. F., & Hopkins, C. R. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.18.10999 · Cited by 172 · see citing works
Wolfsdorf, J. I., & Weinstein, D. A. (2003) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/a:1021831621210 · Cited by 166 · see citing works
Co‐operative regulation of endocytosis by three RAB5 isoforms
Bucci, C., Lütcke, A., Steele‐Mortimer, O., Olkkonen, V. M., Dupree, P., Chiariello, M., Bruni, C. B., Simons, K., & Zerial, M. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)00477-q · Cited by 162 · see citing works
Self-citationRab11a and myosin Vb are required for bile canalicular formation in WIF-B9 cells
Wakabayashi, Y., Dutt, P., Lippincott‐Schwartz, J., & Arias, I. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503702102 · Cited by 159 · see citing works
Lawe, D. C., Chawla, A., Merithew, E., Dumas, J., Carrington, W., Fogarty, K., Lifshitz, L., Tuft, R., Lambright, D., & Corvera, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109239200 · Cited by 156 · see citing works
A subset of yeast vacuolar protein sorting mutants is blocked in one branch of the exocytic pathway
Harsay, E., & Schekman, R. W. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200109077 · Cited by 148 · see citing works
Membrane identity and GTPase cascades regulated by toggle and cut‐out switches
Conte‐Zerial, P. D., Brusch, L., Rink, J. C., Collinet, C., Kalaidzidis, Y. L., Zerial, M., & Deutsch, A. (2008) · Molecular Systems Biology · doi:10.1038/msb.2008.45 · Cited by 129 · see citing works
Self-citationDifferential involvement of endocytic compartments in the biosynthetic traffic of apical proteins
Cresawn, K. O., Potter, B. A., Oztan, A., Guerriero, C. J., Ihrke, G., Goldenring, J. R., Apodaca, G. L., & Weisz, O. A. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601813 · Cited by 118 · see citing works
Wakabayashi, Y., Lippincott‐Schwartz, J., & Arias, I. M. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-10-0737 · Cited by 113 · see citing works
Ihrke, G., Martin, G. V., Shanks, M. R., Schrader, M., Schroer, T. A., & Hubbard, A. L. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.1.115 · Cited by 112 · see citing works
Nokes, R. L., Fields, I. C., Collins, R., & Fölsch, H. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200802176 · Cited by 109 · see citing works
Chen, P.-I., Chen, K., Su, X., & Stahl, P. D. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.034546 · Cited by 104 · see citing works
The maintenance and generation of membrane polarity in hepatocytes
Wang, L., & Boyer, J. L. (2004) · Hepatology · doi:10.1002/hep.20039 · Cited by 103 · see citing works
Regulation of Early Endosomal Entry by theDrosophilaTumor Suppressors Rabenosyn and Vps45
Morrison, H. A., Dionne, H., Rusten, T. E., Brech, A., Fisher, W. W., Pfeiffer, B. D., Celniker, S., Stenmark, H., & Bilder, D. H. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-07-0716 · Cited by 94 · see citing works
Farr, G. A., Hull, M. J., Mellman, I., & Caplan, M. J. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200901021 · Cited by 88 · see citing works
Renaud, G., Hamilton, R. L., & Havel, R. J. (1989) · Hepatology · doi:10.1002/hep.1840090307 · Cited by 85 · see citing works
Recycling endosomes in apical plasma membrane domain formation and epithelial cell polarity
Golachowska, M. R., Hoekstra, D., & van IJzendoorn, S. C. D. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.08.004 · Cited by 79 · see citing works
The fusion of early endosomes induces molecular motor-driven tubule formation and fission.
Skjeldal, F. M., Strunze, S., Bergeland, T., Walseng, E., FGregers, T., & Bakke, O. (2012) · Journal of Cell Science · doi:10.1242/jcs.092569 · Cited by 71 · see citing works
Generation of nonidentical compartments in vesicular transport systems
Heinrich, R., & Rapoport, T. A. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200409087 · Cited by 67 · see citing works
Serio, G., Margaria, V., Jensen, S., Oldani, A., Bártek, J., Bussolino, F., & Lanzetti, L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103516108 · Cited by 56 · see citing works
Shen, H., Ferguson, S. M., Dephoure, N., Park, R. J.-H., Yang, Y., Volpicelli‐Daley, L. A., Gygi, S. P., Schlessinger, J., & Camilli, P. V. D. (2010) · Molecular Biology of the Cell · doi:10.1091/mbc.e10-07-0637 · Cited by 42 · see citing works
Transformational process of the endosomal compartment in nephrocytes of Drosophila melanogaster
Koenig, J. H., & Ikeda, K. (1990) · Cell and Tissue Research · doi:10.1007/bf00309878 · Cited by 42 · see citing works
Endocytosis as an Essential Process in Liver Function and Pathology
Schroeder, B., & McNiven, M. A. (2009) · doi:10.1002/9780470747919.ch7 · Cited by 7 · see citing works
Flagged first, then by citations
1 of the 51 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Signals from the lysosome: a control centre for cellular clearance and energy metabolism
Settembre, C., Fraldi, A., Medina, D. L., & Ballabio, A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3565 · Cited by 1,689 · see citing works
Gilleron, J., Querbes, W., Zeigerer, A., Borodovsky, A., Marsico, G., Schubert, U., Manygoats, K., Seifert, S., Andree, C., Stöter, M., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2612 · Cited by 1,681 · see citing works
Self-citationNew Technologies for Analysis of Extracellular Vesicles
Shao, H., Im, H., Castro, C. M., Breakefield, X. O., Weissleder, R., & Lee, H. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00534 · Cited by 1,672 · see citing works
Organization and execution of the epithelial polarity programme
Rodriguez-Boulan, E. J., & Macara, I. G. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3775 · Cited by 679 · see citing works
Kou, M., Huang, L., Yang, J., Chiang, Z., Chen, S., Liu, J., Guo, L., Zhang, X., Zhou, X., Xu, X. M., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05034-x · Cited by 654 · see citing works
Rab Proteins and the Compartmentalization of the Endosomal System
Wandinger-Ness, A., & Zerial, M. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022616 · Cited by 586 · see citing works
Self-citationHaploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons
Shi, Y., Lin, S., Staats, K. A., Li, Y., Chang, W.-H., Hung, S.-T., Hendricks, E., Linares, G. R., Wang, Y., Son, E. Y., et al. (2018) · Nature Medicine · doi:10.1038/nm.4490 · Cited by 566 · see citing works
CORVET and HOPS tethering complexes – coordinators of endosome and lysosome fusion
Balderhaar, H. J. K., & Ungermann, C. (2013) · Journal of Cell Science · doi:10.1242/jcs.107805 · Cited by 500 · see citing works
Smith, J. J., & Aitchison, J. D. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3700 · Cited by 470 · see citing works
Phosphoinositides as membrane organizers
Posor, Y., Jang, W., & Haucke, V. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00490-x · Cited by 469 · see citing works
Central role for PICALM in amyloid-β blood-brain barrier transcytosis and clearance
Zhao, Z., Sagare, A. P., Ma, Q., Halliday, M. R., Kong, P., Kisler, K., Winkler, E. A., Ramanathan, A., Kanekiyo, T., Bu, G., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4025 · Cited by 410 · see citing works
Rab GTPase Function in Endosome and Lysosome Biogenesis
Langemeyer, L., Fröhlich, F., & Ungermann, C. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.06.007 · Cited by 393 · see citing works
The Complex Ultrastructure of the Endolysosomal SystemPreprint
Klumperman, J., & Raposo, G. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016857 · Cited by 391 · see citing works
Structural and functional hepatocyte polarity and liver disease
Gissen, P., & Arias, I. M. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.06.015 · Cited by 316 · see citing works
Endoplasmic reticulum–endosome contact increases as endosomes traffic and mature
Friedman, J. R., DiBenedetto, J. R., West, M., Rowland, A. A., & Voeltz, G. K. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e12-10-0733 · Cited by 311 · see citing works
Endocytic reawakening of motility in jammed epithelia
Malinverno, C., Corallino, S., Giavazzi, F., Bergert, M., Li, Q., Leoni, M., Disanza, A., Frittoli, E., Oldani, A., Martini, E., et al. (2017) · Nature Materials · doi:10.1038/nmat4848 · Cited by 307 · see citing works
The cell biology of the hepatocyte: A membrane trafficking machine
Schulze, R. J., Schott, M. B., Casey, C. A., Tuma, P. L., & McNiven, M. A. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201903090 · Cited by 246 · see citing works
A Rab5 endosomal pathway mediates Parkin-dependent mitochondrial clearance
Hammerling, B. C., Najor, R. H., Cortez, M. Q., Shires, S. E., Leon, L. J., Gonzalez, E. R., Boassa, D., Phan, S., Thor, A., Jimenez, R. E., et al. (2017) · Nature Communications · doi:10.1038/ncomms14050 · Cited by 216 · see citing works
Krahmer, N., Najafi, B., Schueder, F., Quagliarini, F., Steger, M., Seitz, S., Kasper, R., Salinas, F., Cox, J., Uhlenhaut, N. H., et al. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.09.017 · Cited by 188 · see citing works
Self-citationThe Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy
Hegedűs, K., Takáts, S., Boda, A., Jipa, A., Nagy, P., Varga, K., Kovács, A. L., & Juhász, G. (2016) · Molecular Biology of the Cell · doi:10.1091/mbc.e16-03-0205 · Cited by 207 · see citing works
Recent Advances in Nanostrategies Capable of Overcoming Biological Barriers for Tumor Management
Huo, D., Jiang, X., & Hu, Y. (2019) · Advanced Materials · doi:10.1002/adma.201904337 · Cited by 206 · see citing works
Endocytosis and autophagy: Shared machinery for degradation
Lamb, C. A., Dooley, H. C., & Tooze, S. A. (2012) · BioEssays · doi:10.1002/bies.201200130 · Cited by 183 · see citing works
Braccini, L., Ciraolo, E., Campa, C. C., Perino, A., Longo, D. L., Tibolla, G., Pregnolato, M., Cao, Y., Tassone, B., Damilano, F., et al. (2015) · Nature Communications · doi:10.1038/ncomms8400 · Cited by 175 · see citing works
Palamidessi, A., Malinverno, C., Frittoli, E., Corallino, S., Barbieri, E., Sigismund, S., Beznoussenko, G. V., Martini, E., Garrè, M., Ferrara, I., et al. (2019) · Nature Materials · doi:10.1038/s41563-019-0425-1 · Cited by 175 · see citing works
Appelbaum, J., LaRochelle, J. R., Smith, B. A., Balkin, D. M., Holub, J. M., & Schepartz, A. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.05.022 · Cited by 169 · see citing works
Autophagy and endocytosis – interconnections and interdependencies
Birgisdottir, Å. B., & Johansen, T. (2020) · Journal of Cell Science · doi:10.1242/jcs.228114 · Cited by 170 · see citing works
Endocytosis, Signaling, and BeyondPreprint
Paolo, P., & von Zastrow, M. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016865 · Cited by 169 · see citing works
Endogenously Tagged Rab Proteins: A Resource to Study Membrane Trafficking in Drosophila
Dunst, S., Kazimiers, T., von Zadow, F., Jambor, H. K., Sagner, A., Brankatschk, B., Mahmoud, A., Spannl, S., Tomančák, P., Eaton, S., et al. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.03.022 · Cited by 165 · see citing works
Emerging degrader technologies engaging lysosomal pathways
Ding, Y., Xing, D., Fei, Y., & Lu, B. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00624c · Cited by 162 · see citing works
Role of membrane traffic in the generation of epithelial cell asymmetry
Apodaca, G. L., Gallo, L. I., & Bryant, D. M. (2012) · Nature Cell Biology · doi:10.1038/ncb2635 · Cited by 161 · see citing works
Kremer, K., Kamin, D., Rittweger, E., Wilkes, J., Flammer, H. P., Mahler, S., Heng, J., Tonkin, C. J., Langsley, G., Hell, S. W., et al. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003213 · Cited by 160 · see citing works
Frittoli, E., Palamidessi, A., Marighetti, P., Confalonieri, S., Bianchi, F., Malinverno, C., Mazzarol, G., Viale, G., Martín-Padura, I., Garrè, M., et al. (2014) · The Journal of Cell Biology · doi:10.1083/jcb.201403127 · Cited by 157 · see citing works
Challenges in carrier‐mediated intracellular delivery: moving beyond endosomal barriers
Stewart, M. P., Lorenz, A. S., Dahlman, J. E., & Sahay, G. (2015) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1377 · Cited by 154 · see citing works
The EGFR odyssey – from activation to destruction in space and time
Bakker, J., Spits, M., Neefjes, J., & Berlin, I. (2017) · Journal of Cell Science · doi:10.1242/jcs.209197 · Cited by 152 · see citing works
Class II PI3K Functions in Cell Biology and Disease
Gulluni, F., Santis, M. C. D., Margaria, J. P., Martini, M., & Hirsch, E. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.01.001 · Cited by 152 · see citing works
Costanzo, M., & Zurzolo, C. (2013) · Biochemical Journal · doi:10.1042/bj20121898 · Cited by 151 · see citing works
Regulation of Hepatitis B Virus Infection by Rab5, Rab7, and the Endolysosomal Compartment
Macovei, A., Petrareanu, C., Lazar, C., Florian, P. E., & Branza‐Nichita, N. (2013) · Journal of Virology · doi:10.1128/jvi.00393-13 · Cited by 136 · see citing works
Exosomes in hepatocellular carcinoma: a new horizon
Chen, R., Xu, X., Tao, Y., Qian, Z., & Yu, Y. (2019) · Cell Communication and Signaling · doi:10.1186/s12964-018-0315-1 · Cited by 136 · see citing works
Santiago, F. W., Covaleda, L. M., Sánchez-Aparicio, M. T., Silvas, J. A., Diaz-Vizarreta, A. C., Patel, J. R., Popov, V. L., Yu, X., García‐Sastre, A., & Aguilar, P. V. (2014) · Journal of Virology · doi:10.1128/jvi.03021-13 · Cited by 131 · see citing works
Nanoparticles That Deliver RNA to Bone Marrow Identified by in Vivo Directed Evolution
Sago, C. D., Lokugamage, M. P., Islam, F. Z., Krupczak, B. R., Sato, M., & Dahlman, J. E. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b08976 · Cited by 129 · see citing works
Function and Regulation of the Endosomal Fusion and Fission MachineriesPreprint
Gautreau, A. M., Oguievetskaia, K., & Ungermann, C. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016832 · Cited by 129 · see citing works
Intracellular trafficking and secretion of inflammatory cytokines
Stow, J. L., & Murray, R. Z. (2013) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2013.04.001 · Cited by 128 · see citing works
Cholesterol impairs autophagy-mediated clearance of amyloid beta while promoting its secretion
Barbero-Camps, E., Roca-Agujetas, V., Bartolessis, I., de Dios, C., Fernández-Checa, J. C., Marí, M., Morales, A., Hartmann, T., & Colell, A. (2018) · Autophagy · doi:10.1080/15548627.2018.1438807 · Cited by 125 · see citing works
Early endosome motility spatially organizes polysome distribution
Higuchi, Y., Ashwin, P., Roger, Y., & Steinberg, G. (2014) · The Journal of Cell Biology · doi:10.1083/jcb.201307164 · Cited by 125 · see citing works
Lysosomal signaling in control of degradation pathways.
Huber, L., & Teis, D. (2016) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2016.01.006 · Cited by 121 · see citing works
Cellular Hypoxia Promotes Heterotopic Ossification by Amplifying BMP Signaling
Wang, H., Lindborg, C. M., Lounev, V. Y., Kim, J., McCarrick-Walmsley, R., Xu, M., Mangiavini, L., Groppe, J. C., Shore, E. M., Schipani, E., et al. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2848 · Cited by 125 · see citing works
Vacuolin-1 potently and reversibly inhibits autophagosome-lysosome fusion by activating RAB5A
Lü, Y., Dong, S., Hao, B., Li, C., Zhu, K., Guo, W., Wang, Q., Cheung, K., Wong, C. W. M., Wu, W., et al. (2014) · Autophagy · doi:10.4161/auto.32200 · Cited by 125 · see citing works
Accurate cell segmentation in microscopy images using membrane patterns
Dimopoulos, S., Mayer, C. E., Rudolf, F., & Stelling, J. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu302 · Cited by 122 · see citing works
Recent insights into the molecular pathophysiology of lipid droplet formation in hepatocytes
Sahini, N., & Borlak, J. T. (2014) · Progress in Lipid Research · doi:10.1016/j.plipres.2014.02.002 · Cited by 114 · see citing works
Spatially Restricted G Protein-coupled Receptor Activity via Divergent Endocytic Compartments
Jean‐Alphonse, F., Bowersox, S. L., Chen, S., Beard, G., Puthenveedu, M. A., & Hanyaloglu, A. C. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.526350 · Cited by 110 · see citing works
Membrane Trafficking in Autophagy
Søreng, K., Neufeld, T. P., & Simonsen, A. (2017) · International review of cytology · doi:10.1016/bs.ircmb.2017.07.001 · Cited by 110 · see citing works
Segovia-Miranda, F., Morales-Navarrete, H., Kücken, M., Moser, V., Seifert, S., Repnik, U., Rost, F., Brosch, M., Hendricks, A., Hinz, S., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0660-7 · Cited by 109 · see citing works
Self-citationAutophagy in neurodegenerative diseases: From pathogenic dysfunction to therapeutic modulation
Martínez‐Vicente, M. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.03.005 · Cited by 109 · see citing works
The CORVET complex promotes tethering and fusion of Rab5/Vps21-positive membranes
Balderhaar, H. J. K., Lachmann, J., Yavavli, E., Bröcker, C., Lürick, A., & Ungermann, C. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221785110 · Cited by 106 · see citing works
van de Sluis, B., Wijers, M., & Herz, J. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000411 · Cited by 106 · see citing works
Rab5 and Alsin regulate stress-activated cytoprotective signaling on mitochondria
Hsu, F., Spannl, S., Ferguson, C., Hyman, A. A., Parton, R. G., & Zerial, M. (2018) · eLife · doi:10.7554/elife.32282 · Cited by 105 · see citing works
Self-citationThe biological functions and clinical applications of exosomes in lung cancer
Chen, R., Xu, X., Qian, Z., Zhang, C., Niu, Y., Wang, Z., Sun, J., Zhang, X., & Yu, Y. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03233-y · Cited by 104 · see citing works
Raiborg, C., Schink, K. O., & Stenmark, H. (2013) · FEBS Journal · doi:10.1111/febs.12116 · Cited by 103 · see citing works
Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomes
Villaseñor, R., Nonaka, H., Conte‐Zerial, P. D., Kalaidzidis, Y. L., & Zerial, M. (2015) · eLife · doi:10.7554/elife.06156 · Cited by 103 · see citing works
Self-citationProtein composition of the hepatitis A virus quasi-envelope
McKnight, K. L., Xie, L., González‐López, O., Rivera-Serrano, E. E., Chen, X., & Lemon, S. M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1619519114 · Cited by 102 · see citing works
Hofmann, D., Tenzer, S., Bannwarth, M. B., Messerschmidt, C., Glaser, S.-F., Schild, H., Landfester, K., & Mailänder, V. (2014) · ACS Nano · doi:10.1021/nn502754c · Cited by 101 · see citing works
Spencer, N. Y., & Engelhardt, J. F. (2014) · Biochemistry · doi:10.1021/bi401719r · Cited by 98 · see citing works
Padrissa‐Altés, S., Bachofner, M., Bogorad, R. L., Pohlmeier, L. M., Rossolini, T., Böhm, F., Liebisch, G., Hellerbrand, C., Koteliansky, V., Speicher, T., et al. (2014) · Gut · doi:10.1136/gutjnl-2014-307874 · Cited by 98 · see citing works
Self-citationAutophagy and proteins involved in vesicular trafficking
Sanchez, C. A., Fader, C. M., & Colombo, M. I. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.09.021 · Cited by 97 · see citing works
Endocytosis and early endosome motility in filamentous fungi
Steinberg, G. (2014) · Current Opinion in Microbiology · doi:10.1016/j.mib.2014.04.001 · Cited by 93 · see citing works
Functional properties of hepatocytes in vitro are correlated with cell polarity maintenance
Zeigerer, A., Wuttke, A., Marsico, G., Seifert, S., Kalaidzidis, Y. L., & Zerial, M. (2016) · Experimental Cell Research · doi:10.1016/j.yexcr.2016.11.027 · Cited by 91 · see citing works
Self-citationA Predictive 3D Multi-Scale Model of Biliary Fluid Dynamics in the Liver Lobule
Meyer, K., Ostrenko, O., Bourantas, G., Morales-Navarrete, H., Porat-Shliom, N., Segovia-Miranda, F., Nonaka, H., Ghaemi, A., Verbavatz, J.-M., Brusch, L., et al. (2017) · Cell Systems · doi:10.1016/j.cels.2017.02.008 · Cited by 91 · see citing works
Self-citationMechanisms of apical–basal axis orientation and epithelial lumen positioning
Overeem, A. W., Bryant, D. M., & van IJzendoorn, S. C. D. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.04.002 · Cited by 89 · see citing works
Kalaidzidis, I. V., Miączyńska, M., Brewińska‐Olchowik, M., Hupalowska, A., Ferguson, C., Parton, R. G., Kalaidzidis, Y. L., & Zerial, M. (2015) · The Journal of Cell Biology · doi:10.1083/jcb.201311117 · Cited by 89 · see citing works
Self-citationThe endosomal pathway in Parkinson's disease
Perrett, R. M., Alexopoulou, Z., & Tofaris, G. K. (2015) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2015.02.009 · Cited by 87 · see citing works
Cellular and physiological functions of C9ORF72 and implications for ALS/FTD
Pang, W., & Hu, F. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15255 · Cited by 87 · see citing works
Rab7 Is Functionally Required for Selective Cargo Sorting at the Early Endosome
Girard, E., Chmiest, D., Fournier, N., Johannes, L., Paul, J., Vedie, B., & Lamaze, C. (2013) · Traffic · doi:10.1111/tra.12143 · Cited by 87 · see citing works
Endocytosis in the adaptation to cellular stress
López-Hernández, T., Haucke, V., & Maritzen, T. (2020) · Cell Stress · doi:10.15698/cst2020.10.232 · Cited by 86 · see citing works
Mammalian CORVET Is Required for Fusion and Conversion of Distinct Early Endosome Subpopulations
Perini, E. D., Schaefer, R., Stöter, M., Kalaidzidis, Y. L., & Zerial, M. (2014) · Traffic · doi:10.1111/tra.12232 · Cited by 85 · see citing works
Self-citationBogorad, R. L., Yin, H., Zeigerer, A., Nonaka, H., Ruda, V. M., Zerial, M., Anderson, D. G., & Koteliansky, V. (2014) · Nature Communications · doi:10.1038/ncomms4869 · Cited by 85 · see citing works
Self-citationSpeicher, T., Siegenthaler, B., Bogorad, R. L., Ruppert, R., Petzold, T., Padrissa-Altes, S., Bachofner, M., Anderson, D. G., Koteliansky, V., Fässler, R., et al. (2014) · Nature Communications · doi:10.1038/ncomms4862 · Cited by 85 · see citing works
Self-citationThe Lowe Syndrome Protein OCRL1 Is Required for Endocytosis in the Zebrafish Pronephric Tubule
Oltrabella, F., Pietka, G., Ramirez, I. B.-R., Mironov, A., Starborg, T., Drummond, I. A. S., Hinchliffe, K. A., & Lowe, M. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005058 · Cited by 83 · see citing works
The Roles of Exosomal Proteins: Classification, Function, and Applications
Li, X., Yang, L.-X., Wang, C., Li, H., Shi, D., & Wang, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043061 · Cited by 79 · see citing works
A General Theoretical Framework to Infer Endosomal Network Dynamics from Quantitative Image Analysis
Foret, L., Dawson, J. E., Villaseñor, R., Collinet, C., Deutsch, A., Brusch, L., Zerial, M., Kalaidzidis, Y. L., & Jülicher, F. (2012) · Current Biology · doi:10.1016/j.cub.2012.06.021 · Cited by 78 · see citing works
Self-citationRab GTPases in cilium formation and function
Blacque, O. E., Scheidel, N., & Kuhns, S. (2017) · Small GTPases · doi:10.1080/21541248.2017.1353847 · Cited by 78 · see citing works
Zheng, W. J., Xu, Q., Zhang, Y., Xiaofei, E., Gao, W., Zhang, M., Zhai, W., Rajkumar, R. S., & Liu, Z. (2020) · Virology Journal · doi:10.1186/s12985-020-01463-2 · Cited by 72 · see citing works
Identification of siRNA delivery enhancers by a chemical library screen
Gilleron, J., Paramasivam, P., Zeigerer, A., Querbes, W., Marsico, G., Andree, C., Seifert, S., Amaya, P., Stöter, M., Koteliansky, V., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv762 · Cited by 69 · see citing works
Self-citationMolecular mechanism for Rabex-5 GEF activation by Rabaptin-5
Zhang, Z., Zhang, T., Wang, S., Gong, Z., Tang, C., Chen, J., & Ding, J. (2014) · eLife · doi:10.7554/elife.02687 · Cited by 69 · see citing works
Cargo Sorting in the Endocytic Pathway: A Key Regulator of Cell Polarity and Tissue DynamicsPreprint
Eaton, S., & Martín‐Belmonte, F. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016899 · Cited by 67 · see citing works
HLA-F and MHC-I Open Conformers Cooperate in a MHC-I Antigen Cross-Presentation Pathway
Goodridge, J. P., Lee, N., Burian, A., Pyo, C., Tykodi, S. S., Warren, E. H., Yee, C., Riddell, S. R., & Geraghty, D. E. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300080 · Cited by 66 · see citing works
Chen, X., Sawa, M., & Mobley, W. C. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.10.341 · Cited by 65 · see citing works
Escudero, C. A., Lazo, O. M., Galleguillos, C., Parraguez, J., Lopez-Verrilli, M., Cabeza, C., Leon, L., Saeed, U., Retamal, C., González, A., et al. (2014) · Journal of Cell Science · doi:10.1242/jcs.141754 · Cited by 64 · see citing works
Identification of Trans-Golgi Network Proteins in Arabidopsis thaliana Root Tissue
Groen, A. J., Sáncho-Andrés, G., Breckels, L. M., Gatto, L., Aniento, F., & Lilley, K. S. (2013) · Journal of Proteome Research · doi:10.1021/pr4008464 · Cited by 64 · see citing works
Qin, Y., Deng, Y., Ricketts, C. J., Srikantan, S., Wang, E., Maher, E. R., & Dahia, P. L. M. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt638 · Cited by 63 · see citing works
Role of Intermediate Filaments in Vesicular Traffic
Margiotta, A., & Bucci, C. (2016) · Cells · doi:10.3390/cells5020020 · Cited by 62 · see citing works
Malcomson, B., Wilson, H., Veglia, E., Thillaiyampalam, G., Barsden, R., Donegan, S., Elbanna, A., Elborn, J. S., Ennis, M., Kelly, C., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520289113 · Cited by 62 · see citing works
Role of protein kinase C isoforms in bile formation and cholestasis
Anwer, S. M. (2014) · Hepatology · doi:10.1002/hep.27088 · Cited by 61 · see citing works
Hepatitis C Virus Induces the Localization of Lipid Rafts to Autophagosomes for Its RNA Replication
Kim, J. Y., Wang, L., Lee, J., & Ou, J. J. (2017) · Journal of Virology · doi:10.1128/jvi.00541-17 · Cited by 61 · see citing works
The ABCG2/BCRP transporter and its variants – from structure to pathology
Sarkadi, B., Homolya, L., & Hegedűs, T. (2020) · FEBS Letters · doi:10.1002/1873-3468.13947 · Cited by 61 · see citing works
Liquid-crystal organization of liver tissue
Morales-Navarrete, H. A., Nonaka, H., Scholich, A., Segovia‐Miranda, F., de Back, W., Meyer, K., Bogorad, R. L., Koteliansky, V., Brusch, L., Kalaidzidis, Y. L., et al. (2019) · eLife · doi:10.7554/elife.44860 · Cited by 60 · see citing works
Self-citationZang, Y., Wan, M., Liu, M., Ke, H., Ma, S., Liu, L., Ni, J., & Pastor-Pareja, J. C. (2015) · eLife · doi:10.7554/elife.07187 · Cited by 60 · see citing works
Rab GTPase signaling in neurite outgrowth and axon specification
Villarroel‐Campos, D., Bronfman, F. C., & González-Billault, C. E. (2016) · Cytoskeleton · doi:10.1002/cm.21303 · Cited by 60 · see citing works
Rab11 and phosphoinositides: A synergy of signal transducers in the control of vesicular trafficking
Campa, C. C., & Hirsch, E. (2016) · Advances in Biological Regulation · doi:10.1016/j.jbior.2016.09.002 · Cited by 60 · see citing works
Phosphoinositide 3-kinase (PI3K) classes: From cell signaling to endocytic recycling and autophagy
Safaroghli‐Azar, A., Sanaei, M., Pourbagheri‐Sigaroodi, A., & Bashash, D. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175827 · Cited by 58 · see citing works
Research Progress on the Mechanism of Nanoparticles Crossing the Intestinal Epithelial Cell Membrane
He, Y., Cheng, M., Yang, R., Li, H., Lu, Z., Jin, Y., Feng, J., & Tu, L. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15071816 · Cited by 59 · see citing works
- Authors
- Zeigerer, A., Gilleron, J., Bogorad, R. L., Marsico, G., Nonaka, H., Seifert, S., Epstein-Barash, H., Kuchimanchi, S., Peng, C. G., Ruda, V. M., Conte-Zerial, P. D., Hengstler, J. G., Kalaidzidis, Y., Koteliansky, V., & Zerial, M.
- Affiliations
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- Koch Institute for Integrative Cancer Research At MIT (US)
- Alnylam Pharmaceuticals (United States) (US)
- Harvard University (US)
- Leibniz Research Centre for Working Environment and Human Factors (DE)
- Lomonosov Moscow State University (RU)
- Corresponding author
- Zerial, Marino
- ORCID
- Venue
- Nature
- Published
- 2012-05
- Volume
- 485
- Issue
- 7399
- Pages
- 465-470
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1967182910
- Cited by
- 362
- References
- 51
- Citations by year
- 2026: 9 · 2025: 25 · 2024: 21 · 2023: 17 · 2022: 20 · 2021: 35 · 2020: 22 · 2019: 31 · 2018: 15 · 2017: 30 · 2016: 20 · 2015: 31 · 2014: 47 · 2013: 29 · 2012: 10
- FWCI
- 17.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Site cant be reached (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- Rab5, endolysosomal system, small GTPases, endocytosis, early endosomes, late endosomes, lysosomes, hepatocyte polarity, bile canaliculi, mathematical modeling, RNA interference, mouse liver, serum cholesterol
- MeSH terms
- Animals, Cells, Cultured, Endocytosis, Isoenzymes, Lipoproteins, LDL, Liver, Lysosomes, Organ Specificity, Endosomes, RNA, Messenger, Time Factors, Protein Biosynthesis, Cell Polarity, rab5 GTP-Binding Proteins, Hepatocytes, Vesicular Transport Proteins, RNA Interference, Mice, Gene Knockdown Techniques, Multivesicular Bodies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
