CoChat
Sign Up
Cited by 87

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

RUFY3 links Arl8b and JIP4-Dynein complex to regulate lysosome size and positioning

Kumar, Gaurav, Chawla, Prateek, Dhiman, Neha, Chadha, Sanya, Sharma, Sheetal, Sethi, Kanupriya, Sharma, Mahak, Tuli, Amit·2022·Nature Communications
DOI 10.1038/s41467-022-29077-yPMC PMC8938454

Published version of a preprint

Open this paper in CoChat — free account

Abstract

The bidirectional movement of lysosomes on microtubule tracks regulates their whole-cell spatial arrangement. Arl8b, a small GTP-binding (G) protein, promotes lysosome anterograde trafficking mediated by kinesin-1. Herein, we report an Arl8b effector, RUFY3, which regulates the retrograde transport of lysosomes. We show that RUFY3 interacts with the JIP4-dynein-dynactin complex and facilitates Arl8b association with the retrograde motor complex. Accordingly, RUFY3 knockdown disrupts the positioning of Arl8b-positive endosomes and reduces Arl8b colocalization with Rab7-marked late endosomal compartments. Moreover, we find that RUFY3 regulates nutrient-dependent lysosome distribution, although autophagosome-lysosome fusion and autophagic cargo degradation are not impaired upon RUFY3 depletion. Interestingly, lysosome size is significantly reduced in RUFY3 depleted cells, which could be rescued by inhibition of the lysosome reformation regulatory factor PIKFYVE. These findings suggest a model in which the perinuclear cloud arrangement of lysosomes regulates both the positioning and size of these proteolytic compartments.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-022-29077-y

Cites

8 of 8 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 73

  1. Ballabio, A. & Bonifacino, J. S. Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat. Rev. Mol. Cell Biol. 21, 101–118 (2020). · DOI · Paper page
  2. Bright, N. A., Davis, L. J. & Luzio, J. P. Endolysosomes are the principal intracellular sites of acid hydrolase activity. Curr. Biol. 26, 2233–2245 (2016). · DOI
  3. Huotari, J. & Helenius, A. Endosome maturation. EMBO J. 30, 3481–3500 (2011). · DOI
  4. Bissig, C., Hurbain, I., Raposo, G. & van Niel, G. PIKfyve activity regulates reformation of terminal storage lysosomes from endolysosomes. Traffic 18, 747–757 (2017). · DOI
  5. Jongsma, M. L. et al. An ER-associated pathway defines endosomal architecture for controlled cargo transport. Cell 166, 152–166 (2016). · DOI
  6. Cabukusta, B. & Neefjes, J. Mechanisms of lysosomal positioning and movement. Traffic 19, 761–769 (2018). · DOI
  7. Korolchuk, V. I. et al. Lysosomal positioning coordinates cellular nutrient responses. Nat. Cell Biol. 13, 453–460 (2011). · DOI · Paper page
  8. Tuli, A. et al. Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell-mediated cytotoxicity. Mol. Biol. Cell 24, 3721–3735 (2013). · DOI
  9. Laopanupong, T. et al. Lysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain. Sci. Rep. 11, 4342 (2021). · DOI
  10. Bonifacino, J. S. & Neefjes, J. Moving and positioning the endolysosomal system. Curr. Opin. Cell Biol. 47, 1–8 (2017). · DOI · Paper page
  11. Saric, A. et al. mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells. Mol. Biol. Cell 27, 321–333 (2016). · DOI
  12. Takemasu, S. et al. Phosphorylation of TMEM55B by Erk/MAPK regulates lysosomal positioning. J. Biochem. 166, 175–185 (2019). · DOI · Paper page
  13. Kimura, S., Noda, T. & Yoshimori, T. Dynein-dependent movement of autophagosomes mediates efficient encounters with lysosomes. Cell Struct. Funct. 33, 109–122 (2008). · DOI · Paper page
  14. Jia, R. & Bonifacino, J. S. Lysosome positioning influences mTORC2 and AKT signaling. Mol. Cell 75, 26–38 e23 (2019). · DOI
  15. Lu, M. et al. The structure and global distribution of the endoplasmic reticulum network are actively regulated by lysosomes. Sci. Adv. https://doi.org/10.1126/sciadv.abc7209 (2020). · DOI
  16. Spits, M. et al. Mobile late endosomes modulate peripheral endoplasmic reticulum network architecture. EMBO Rep. https://doi.org/10.15252/embr.202050815 (2021). · DOI
  17. Schiefermeier, N. et al. The late endosomal p14-MP1 (LAMTOR2/3) complex regulates focal adhesion dynamics during cell migration. J. Cell Biol. 205, 525–540 (2014). · DOI
  18. Rabanal-Ruiz, Y. et al. mTORC1 activity is supported by spatial association with focal adhesions. J. Cell Biol. https://doi.org/10.1083/jcb.202004010 (2021). · DOI
  19. Hunt, S. D. & Stephens, D. J. The role of motor proteins in endosomal sorting. Biochem. Soc. Trans. 39, 1179–1184 (2011). · DOI
  20. Homma, Y., Hiragi, S. & Fukuda, M. Rab family of small GTPases: an updated view on their regulation and functions. FEBS J. 288, 36–55 (2021). · DOI
  21. Kjos, I., Vestre, K., Guadagno, N. A., Borg Distefano, M. & Progida, C. Rab and Arf proteins at the crossroad between membrane transport and cytoskeleton dynamics. Biochim. Biophys. Acta Mol. Cell Res. 1865, 1397–1409 (2018). · DOI
  22. Donaldson, J. G. & Jackson, C. L. ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat. Rev. Mol. Cell Biol. 12, 362–375 (2011). · DOI
  23. Jordens, I. et al. The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors. Curr. Biol. 11, 1680–1685 (2001). · DOI · Paper page
  24. Pankiv, S. et al. FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end-directed vesicle transport. J. Cell Biol. 188, 253–269 (2010). · DOI
  25. Khatter, D., Sindhwani, A. & Sharma, M. Arf-like GTPase Arl8: Moving from the periphery to the center of lysosomal biology. Cell Logist. 5, e1086501 (2015). · DOI
  26. Hofmann, I. & Munro, S. An N-terminally acetylated Arf-like GTPase is localised to lysosomes and affects their motility. J. Cell Sci. 119, 1494–1503 (2006). · DOI
  27. Rosa-Ferreira, C. & Munro, S. Arl8 and SKIP act together to link lysosomes to kinesin-1. Dev. Cell 21, 1171–1178 (2011). · DOI · Paper page
  28. Marwaha, R. et al. The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traffic to lysosomes. J. Cell Biol. 216, 1051–1070 (2017). · DOI
  29. Guardia, C. M., Farias, G. G., Jia, R., Pu, J. & Bonifacino, J. S. BORC functions upstream of kinesins 1 and 3 to coordinate regional movement of lysosomes along different microtubule tracks. Cell Rep. 17, 1950–1961 (2016). · DOI · Paper page
  30. Michelet, X. et al. Lysosome-mediated plasma membrane repair is dependent on the small GTPase Arl8b and determines cell death type in Mycobacterium tuberculosis infection. J. Immunol. 200, 3160–3169 (2018). · DOI
  31. Pu, J., Keren-Kaplan, T. & Bonifacino, J. S. A ragulator-BORC interaction controls lysosome positioning in response to amino acid availability. J. Cell Biol. 216, 4183–4197 (2017). · DOI
  32. Pu, J. et al. BORC, a multisubunit complex that regulates lysosome positioning. Dev. Cell 33, 176–188 (2015). · DOI · Paper page
  33. Mrakovic, A., Kay, J. G., Furuya, W., Brumell, J. H. & Botelho, R. J. Rab7 and Arl8 GTPases are necessary for lysosome tubulation in macrophages. Traffic 13, 1667–1679 (2012). · DOI · Paper page
  34. Sindhwani, A. et al. Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication. PLoS Pathog. 13, e1006700 (2017). · DOI
  35. Tuli, A. & Sharma, M. How to do business with lysosomes: Salmonella leads the way. Curr. Opin. Microbiol. 47, 1–7 (2019). · DOI
  36. Ghosh, S. et al. beta-Coronaviruses use lysosomes for egress instead of the biosynthetic secretory pathway. Cell 183, 1520–1535 e1514 (2020). · DOI
  37. Kesisova, I. A., Robinson, B. P. & Spiliotis, E. T. A septin GTPase scaffold of dynein-dynactin motors triggers retrograde lysosome transport. J. Cell Biol. https://doi.org/10.1083/jcb.202005219 (2021). · DOI
  38. Char, R. & Pierre, P. The RUFYs, a family of effector proteins involved in intracellular trafficking and cytoskeleton dynamics. Front. Cell Dev. Biol. 8, 779 (2020). · DOI
  39. Honda, A., Usui, H., Sakimura, K. & Igarashi, M. Rufy3 is an adapter protein for small GTPases that activates a Rac guanine nucleotide exchange factor to control neuronal polarity. J. Biol. Chem. 292, 20936–20946 (2017). · DOI
  40. Kitagishi, Y. & Matsuda, S. RUFY, Rab and Rap family proteins involved in a regulation of cell polarity and membrane trafficking. Int J. Mol. Sci. 14, 6487–6498 (2013). · DOI
  41. Mori, T., Wada, T., Suzuki, T., Kubota, Y. & Inagaki, N. Singar1, a novel RUN domain-containing protein, suppresses formation of surplus axons for neuronal polarity. J. Biol. Chem. 282, 19884–19893 (2007). · DOI
  42. Wang, G. et al. PAK1 regulates RUFY3-mediated gastric cancer cell migration and invasion. Cell Death Dis. https://doi.org/10.1038/cddis.2015.50 (2015). · DOI
  43. Xie, R. et al. Rufy3 promotes metastasis through epithelial-mesenchymal transition in colorectal cancer. Cancer Lett. 390, 30–38 (2017). · DOI
  44. Abu-Remaileh, M. et al. Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes. Science 358, 807–813 (2017). · DOI
  45. Jongsma, M. L. et al. SKIP-HOPS recruits TBC1D15 for a Rab7-to-Arl8b identity switch to control late endosome transport. EMBO J. 39, e102301 (2020). · DOI
  46. Garg, S. et al. Lysosomal trafficking, antigen presentation, and microbial killing are controlled by the Arf-like GTPase Arl8b. Immunity 35, 182–193 (2011). · DOI
  47. Khatter, D. et al. The small GTPase Arl8b regulates assembly of the mammalian HOPS complex on lysosomes. J. Cell Sci. 128, 1746–1761 (2015).
  48. Keren-Kaplan, T. & Bonifacino, J. S. ARL8 relieves SKIP autoinhibition to enable coupling of lysosomes to kinesin-1. Curr. Biol. 31, 540–554 e545 (2021). · DOI
  49. Rishal, I. et al. A motor-driven mechanism for cell-length sensing. Cell Rep. 1, 608–616 (2012). · DOI
  50. Reck-Peterson, S. L., Redwine, W. B., Vale, R. D. & Carter, A. P. The cytoplasmic dynein transport machinery and its many cargoes. Nat. Rev. Mol. Cell Biol. 19, 382–398 (2018). · DOI
  51. Ponsford, A. H. et al. Live imaging of intra-lysosome pH in cell lines and primary neuronal culture using a novel genetically encoded biosensor. Autophagy https://doi.org/10.1080/15548627.2020.1771858 (2020). · DOI
  52. Ma, L., Ouyang, Q., Werthmann, G. C., Thompson, H. M. & Morrow, E. M. Live-cell microscopy and fluorescence-based measurement of luminal pH in intracellular organelles. Front. Cell Dev. Biol. 5, 71 (2017). · DOI
  53. Guha, S. et al. Approaches for detecting lysosomal alkalinization and impaired degradation in fresh and cultured RPE cells: evidence for a role in retinal degenerations. Exp. Eye Res. 126, 68–76 (2014). · DOI
  54. Diwu, Z., Chen, C. S., Zhang, C., Klaubert, D. H. & Haugland, R. P. A novel acidotropic pH indicator and its potential application in labeling acidic organelles of live cells. Chem. Biol. 6, 411–418 (1999). · DOI
  55. Yordanov, T. E. et al. Biogenesis of lysosome-related organelles complex-1 (BORC) regulates late endosomal/lysosomal size through PIKfyve-dependent phosphatidylinositol-3,5-bisphosphate. Traffic 20, 674–696 (2019). · DOI
  56. Choy, C. H. et al. Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence. J. Cell Sci. https://doi.org/10.1242/jcs.213587 (2018). · DOI
  57. Saffi, G. T. & Botelho, R. J. Lysosome fission: planning for an exit. Trends Cell Biol. 29, 635–646 (2019). · DOI
  58. Sharma, G. et al. A family of PIKFYVE inhibitors with therapeutic potential against autophagy-dependent cancer cells disrupt multiple events in lysosome homeostasis. Autophagy 15, 1694–1718 (2019). · DOI
  59. Jia, R., Guardia, C. M., Pu, J., Chen, Y. & Bonifacino, J. S. BORC coordinates encounter and fusion of lysosomes with autophagosomes. Autophagy 13, 1648–1663 (2017). · DOI · Paper page
  60. Meneses-Salas, E. et al. Selective degradation permits a feedback loop controlling annexin A6 and cholesterol levels in endolysosomes of NPC1 mutant cells. Cells https://doi.org/10.3390/cells9051152 (2020). · DOI
  61. Keren-Kaplan, T. etal. RUFY3 and RUFY4 are ARL8 effectors that couple lysosomes to dynein-dynactin. Preprint (Version 1) at Res. Sq. https://doi.org/10.21203/rs.3.rs-469512/v1 (2021). · DOI
  62. Cason, S. E. et al. Sequential dynein effectors regulate axonal autophagosome motility in a maturation-dependent pathway. J. Cell Biol. https://doi.org/10.1083/jcb.202010179 (2021). · DOI
  63. Cheng, X. T. et al. Characterization of LAMP1-labeled nondegradative lysosomal and endocytic compartments in neurons. J. Cell Biol. 217, 3127–3139 (2018). · DOI · Paper page
  64. Marchesin, V. et al. ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion. J. Cell Biol. 211, 339–358 (2015). · DOI · Paper page
  65. Sapmaz, A. et al. USP32 regulates late endosomal transport and recycling through deubiquitylation of Rab7. Nat. Commun. 10, 1454 (2019). · DOI
  66. Rojas, R. et al. Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7. J. Cell Biol. 183, 513–526 (2008). · DOI · Paper page
  67. Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012). · DOI · Paper page
  68. Pedersen, N. M. et al. Protrudin-mediated ER-endosome contact sites promote MT1-MMP exocytosis and cell invasion. J. Cell Biol. https://doi.org/10.1083/jcb.202003063 (2020). · DOI
  69. Hong, Z. et al. PtdIns3P controls mTORC1 signaling through lysosomal positioning. J. Cell Biol. 216, 4217–4233 (2017). · DOI
  70. Joseph, J., Tan, S. H., Karpova, T. S., McNally, J. G. & Dasso, M. SUMO-1 targets RanGAP1 to kinetochores and mitotic spindles. J. Cell Biol. 156, 595–602 (2002). · DOI
  71. Tinevez, J. Y. et al. TrackMate: an open and extensible platform for single-particle tracking. Methods 115, 80–90 (2017). · DOI
  72. Kumar, G., Arya, S. B. & Tuli, A. Method for studying the effect of gene silencing on bacterial infection-induced ERK1/2 signaling in bone-marrow derived macrophages. Bio Protoc. https://doi.org/10.21769/BioProtoc.3123 (2018). · DOI
  73. Sharma, A. et al. Methods for binding analysis of small GTP-binding proteins with their effectors. Methods Cell Biol. 166, 235–250 (2021). · DOI

Cited by

Sorted by citations

Metadata

Authors
Kumar, G., Chawla, P., Dhiman, N., Chadha, S., Sharma, S., Sethi, K., Sharma, M., & Tuli, A.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2022-03-21
Volume
13
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-022-29077-y
PMC
PMC8938454
Cited by
87
References
8
Language
en
Licence
Funders
DBT India Alliance (IA/S/19/1/504270, IA/I/14/2/501543)

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