The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“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]
Citations
Cites
Rab proteins as membrane organizers
Zerial, M., & McBride, H. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35052055 · Cited by 3,381
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
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 1,908
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
Self-citationThe Liver: Biology and Pathobiology.
(1983) · Annals of Internal Medicine · doi:10.7326/0003-4819-98-5-690_3 · Cited by 1,615
ENDOCYTOSIS AND MOLECULAR SORTING
Mellman, I. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.575 · Cited by 1,551
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 1,398
Self-citationMukherjee, S., Ghosh, R. K., & Maxfield, F. R. (1997) · Physiological Reviews · doi:10.1152/physrev.1997.77.3.759 · Cited by 1,299
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
Self-citationA combinatorial library of lipid-like materials for delivery of RNAi therapeutics
Akinc, A., Zumbuehl, A., Goldberg, M., Leshchiner, E. S., Busini, V., Hossain, N., Bacallado, S. A., Nguyen, D. N., Fuller, J., Alvarez, R., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1402 · Cited by 1,150
Self-citation
Flagged first, then by citations
1 of the 51 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 301–361 of 361
Identification of Rab GTPase ‐Activating Proteins Required for Tubular Endosome Formation
Nakashima, S., & Fukuda, M. (2025) · Traffic · doi:10.1111/tra.70007 · Cited by 1
Love, M., Dang, R. C., Xie, J., & Zhang, P. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2524765123 · Cited by 1
Exosome Biogenesis: Meta-Analysis of Intraluminal Vesicle Size Across Species
Ghosal, S., Leporati, R., Yilmaz, B., Kestecher, B. M., Bodnár, B. R., Fattah, M. A., Menna, L., Takács, A., Hegyesi, H., Kőhidai, L., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27073176 · Cited by 1
Zuo, X., Chen, Z., Chen, X., Guan, D., Shaw, P. X., Johnstone, A. D., Becker, A., Das, U., & Mobley, W. C. (2026) · npj Parkinson s Disease · doi:10.1038/s41531-026-01382-z · Cited by 1
The young and happy marriage of membrane traffic and cell polarity
Thompson, B. J., Perez, F., & Vaccari, T. (2012) · EMBO Reports · doi:10.1038/embor.2012.98 · Cited by 1
Rab Proteins and the Organization of Organelle Membrane Domains
Wieffer, M., McShane, M. P., & Zerial, M. (2014) · Springer eBooks · doi:10.1007/978-3-319-07761-1_2 · Cited by 1
Self-citationMembrane Trafficking Mechanisms: Exocytosis and Endocytosis in Dendrites
Winckler, B. (2016) · Springer eBooks · doi:10.1007/978-4-431-56050-0_4 · Cited by 1
BAR domain is essential for early endosomal trafficking and dynamics in Ascochyta rabiei
Shree, A., Sinha, M., & Verma, P. K. (2023) · 3 Biotech · doi:10.1007/s13205-022-03451-5 · Cited by 1
Mitev, L. (2022) · Mediterranean Journal of Hematology and Infectious Diseases · doi:10.4084/mjhid.2022.079 · Cited by 1
Chantarasinlapin, P. (2017) · FIU - Digital Commons (Florida International University) · doi:10.25148/etd.fidc001744 · Cited by 1
Theory of Cargo and Membrane Trafficking
Foret, L., Brusch, L., & Jülicher, F. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-394447-4.40009-x · Cited by 1
Axonal mTOR–dependent Rab5 translation drives axonal transport and BDNF signaling to the nucleusPreprint
Tiburcio‐Félix, R., Tapia-Peralta, C., Ahumada-Montalva, P., Arriagada, G., Perlson, E., & Bronfman, F. C. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.14.682461 · Cited by 2
Theory of Cargo and Membrane Trafficking
Foret, L., Brusch, L., & Jülicher, F. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-821618-7.40009-x
The virtual liver: possibilities to simulate mechanisms of toxicity and predict drug targets
Hengstler, J. G. (2013) · Toxicology Letters · doi:10.1016/j.toxlet.2013.06.029
Self-citationSociaux, S. S. (2019)
NEUTROPHIL SECRETION OF THE PROINFLAMMATORY CYTOKINE TNF VIA RECYCLING ENDOSOMES
Srivastava, N. (2015) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r32f7jz18
Kratzke, M. (2012) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-3298
Yambire, K. F. (2018) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-7142
The early endosomal protein Rab21 is critical for enterocyte functions and intestinal homeostasisPreprint
Nassari, S., Lévesque, D., Boisvert, F., & Jean, S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.18.378984
Anisotropic expansion of hepatocyte lumina enforced by apical bulkheadsPreprint
Belicová, L., Repnik, U., Delpierre, J., Gralinska, E., Seifert, S., Valenzuela, J. I., Morales-Navarrete, H. A., Franke, C., Räägel, H., Shcherbinina, E. Y., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.31.424978
Self-citationMitochondrial dysfunction and autophagy in neurodegeneration
Gupta, R. V., Ambasta, R. K., & Kumar, P. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-85666-9.00019-x
Endosome to Lysosome Transport
Bucci, C., & Guerra, F. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821618-7.00056-0
Understanding Pikfyve Control Of Lysome Dynamics
Saffi, G. T. (2021) · doi:10.32920/ryerson.14651847
Tissue Remodeling in Health and Disease Caused by Bacteria, Parasites, Fungi, and Viruses
(2021) · Frontiers research topics · doi:10.3389/978-2-88966-580-8
Akhmanova, A. S. (2014) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718264293.793490930
Paul, F., Ng, C., Sahari, U. B. M., Nafissi, S., Nilipoor, Y., Tavasoli, A. R., Bonnard, C., Wong, P., Nabavizadeh, N., Altunoğlu, U., et al. (2022) · Human Molecular Genetics · doi:10.1093/hmg/ddac120
A Drosophila Arl8 kis GTPáz szerepe a lizoszomális fúziós folyamatokban
Boda, A. (2020) · Eötvös Loránd Tudományegyetem · doi:10.15476/elte.2020.141
Rme-6 integrates EGFR trafficking and signalling to regulate ERK1/2 signalosome dynamicsPreprint
Alshahrani, F., Zhu, Z., Ferreira, F., McComb, A., Maib, H., Pruzina, S., Robinson, D. A., Murray, D. H., & Smythe, E. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.05.539436
Spatiotemporal recruitment of the ubiquitin-specific protease USP8 directs endosome maturationPreprint
Miao, Y., Du, Y., Wang, B., Liang, J., Yu, L., Dang, S., Liu, J., Li, D., He, K., & Ding, M. (2024) · eLife · doi:10.7554/elife.96353.1
Spatiotemporal recruitment of the ubiquitin-specific protease USP8 directs endosome maturationPreprint
Miao, Y., Du, Y., Wang, B., Liang, J., Yu, L., Dang, S., Liu, J., Li, D., He, K., & Ding, M. (2024) · eLife · doi:10.7554/elife.96353.2
Miao, Y., Du, Y., Wang, B., Liang, J., Yu, L., Dang, S., Liu, J., Li, D., He, K., & Ding, M. (2024) · eLife · doi:10.7554/elife.96353.2.sa4
Spatiotemporal recruitment of the ubiquitin-specific protease USP8 directs endosome maturationPreprint
Miao, Y., Du, Y., Wang, B., Liang, J., Yu, L., Dang, S., Liu, J., Li, D., He, K., & Ding, M. (2024) · eLife · doi:10.7554/elife.96353.3
Chronis, I. B., Vistein, R., Gokhale, A., Faúndez, V., & Puthenveedu, M. A. (2024) · Molecular Pharmacology · doi:10.1124/molpharm.124.000939
Mohamed, E., Goodman, S., Cooksey, L., Fletcher, D. M., Dean, O., Boncheva, V., Mills, K., Orchard, K. H., & Guinn, B. (2025) · Onco · doi:10.3390/onco5020019
LncRNA Xist acts as a miR-486-5p sponge to modulate myoblast proliferation by recruiting Stk4
Wang, W., Yan, H., Li, W., Chaohang, Y., Shengcai, W., Xioqing, C., Nanqing, Z., Qing, Y., Qianmin, H., Feng, Z., et al. (2025) · Journal of Muscle Research and Cell Motility · doi:10.1007/s10974-025-09708-9
Lipopolysaccharide stimulates dynamic changes in B cell metabolism to promote proliferationPreprint
Cheung, D. M., Razsolkov, M., Bonacina, F., Andrews, S., Sumoreeah, M., Sinclair, L. V., Howden, A. J. M., & Arthur, J. S. C. (2025) · eLife · doi:10.7554/elife.109093
Rab10 plays a protective role in the development of pathological cardiac hypertrophy
Xu, F., Wu, M., Wang, Y., Luo, H., Gao, X., Lai, S., & Lu, C. (2025) · Journal of Molecular and Cellular Cardiology Plus · doi:10.1016/j.jmccpl.2025.100494
Endosome-associated Rab GTPases control distinct aspects of neural circuit assemblyPreprint
Dong, K. X., Zhang, Y., Ji, H., Luginbuhl, D. J., Luo, L., & McLaughlin, C. N. (2025) · eLife · doi:10.7554/elife.109394
Endosome-associated Rab GTPases control distinct aspects of neural circuit assemblyPreprint
Dong, K. X., Ji, H., Luginbuhl, D. J., Luo, L., & McLaughlin, C. N. (2025) · eLife · doi:10.7554/elife.109394.1
Additional file 1 of The ESCRT-III molecules regulate the apical targeting of bile salt export pump
Wu, S.-H., Chang, M.-H., Chen, Y.-H., Wu, H.-L., Chua, H.-H., Chien, C.-S., Ni, Y.-H., Chen, H.-L., & Chen, H.-L. (2021) · Figshare · doi:10.6084/m9.figshare.14189573
Additional file 2 of The ESCRT-III molecules regulate the apical targeting of bile salt export pump
Wu, S.-H., Chang, M.-H., Chen, Y.-H., Wu, H.-L., Chua, H.-H., Chien, C.-S., Ni, Y.-H., Chen, H.-L., & Chen, H.-L. (2021) · Figshare · doi:10.6084/m9.figshare.14189576
Rab5 hyperactivation: The central hub for endolysosomal dysfunction in Down syndrome
Chen, X. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-25-00967
Yan, X., Hu, T., Tang, T., Ma, X., Wang, J., Zhou, W., & Liu, H. (2026) · Virology · doi:10.1016/j.virol.2026.110891
The Scrib1 Interactome and its relevance for synaptic plasticity & neurodevelopmental disorders
Pinheiro, V. L. M. (2014) · theses.fr (ABES) · doi:10.70675/b1c2e418zac9cz44c5zb050z72f9b6a47586
Chassagne, J. (2019) · theses.fr (ABES) · doi:10.70675/74df0299z4167z4397zb93fz28bc889326f4
Endosome-associated Rab GTPases control distinct aspects of neural circuit assemblyPreprint
Dong, K. X., Zhang, Y., Ji, H., Luginbuhl, D. J., Luo, L., & McLaughlin, C. N. (2026) · eLife · doi:10.7554/elife.109394.2
Gil‐Lozano, M., Simoes, E., Wu, M., Wiedemann, T., 권윤, Sekar, R., Morigny, P., Troullinaki, M., Merl‐Pham, J., Buettner, M., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-77808-2
Self-citationIron Homeostasis and Liver Diseases
Yang, P., Shi, Z. X., Huang, Q., Tu, Z., Sun, Y., Wang, L., & Wei, Y. (2026) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.71412
Metadata
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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
