A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting

Endosomes are specialized organelles that function in the secretory and endocytic protein sorting pathways. Endocytosed cell surface receptors and transporters destined for lysosomal degradation are sorted into intraluminal vesicles (ILVs) at endosomes by endosomal sorting complexes required for tra...

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Main Authors: Suzuki, Sho W., West, Matthew, Zhang, Yichen, Fan, Jenny S., Roberts, Rachel T., Odorizzi, Greg, Emr, Scott D.
Other Authors: School of Biological Sciences
Format: Journal Article
Language:English
Published: 2024
Subjects:
Online Access:https://hdl.handle.net/10356/175617
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author Suzuki, Sho W.
West, Matthew
Zhang, Yichen
Fan, Jenny S.
Roberts, Rachel T.
Odorizzi, Greg
Emr, Scott D.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Suzuki, Sho W.
West, Matthew
Zhang, Yichen
Fan, Jenny S.
Roberts, Rachel T.
Odorizzi, Greg
Emr, Scott D.
author_sort Suzuki, Sho W.
collection NTU
description Endosomes are specialized organelles that function in the secretory and endocytic protein sorting pathways. Endocytosed cell surface receptors and transporters destined for lysosomal degradation are sorted into intraluminal vesicles (ILVs) at endosomes by endosomal sorting complexes required for transport (ESCRT) proteins. The endosomes (multivesicular bodies, MVBs) then fuse with the lysosome. During endosomal maturation, the number of ILVs increases, but the size of endosomes does not decrease despite the consumption of the limiting membrane during ILV formation. Vesicle-mediated trafficking is thought to provide lipids to support MVB biogenesis. However, we have uncovered an unexpected contribution of a large bridge-like lipid transfer protein, Vps13, in this process. Here, we reveal that Vps13-mediated lipid transfer at ER-endosome contact sites is required for the ESCRT pathway. We propose that Vps13 may play a critical role in supplying lipids to the endosome, ensuring continuous ESCRT-mediated sorting during MVB biogenesis.
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spelling ntu-10356/1756172024-05-06T15:32:09Z A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting Suzuki, Sho W. West, Matthew Zhang, Yichen Fan, Jenny S. Roberts, Rachel T. Odorizzi, Greg Emr, Scott D. School of Biological Sciences Medicine, Health and Life Sciences Endocytosis Endosome Endosomes are specialized organelles that function in the secretory and endocytic protein sorting pathways. Endocytosed cell surface receptors and transporters destined for lysosomal degradation are sorted into intraluminal vesicles (ILVs) at endosomes by endosomal sorting complexes required for transport (ESCRT) proteins. The endosomes (multivesicular bodies, MVBs) then fuse with the lysosome. During endosomal maturation, the number of ILVs increases, but the size of endosomes does not decrease despite the consumption of the limiting membrane during ILV formation. Vesicle-mediated trafficking is thought to provide lipids to support MVB biogenesis. However, we have uncovered an unexpected contribution of a large bridge-like lipid transfer protein, Vps13, in this process. Here, we reveal that Vps13-mediated lipid transfer at ER-endosome contact sites is required for the ESCRT pathway. We propose that Vps13 may play a critical role in supplying lipids to the endosome, ensuring continuous ESCRT-mediated sorting during MVB biogenesis. Published version S.W. Suzuki is supported by Osamu Hayaishi Memorial Scholarship for Study Abroad. This work was supported by a Cornell University Research Grant (CU563704) to S.D. 2024-04-30T07:16:05Z 2024-04-30T07:16:05Z 2024 Journal Article Suzuki, S. W., West, M., Zhang, Y., Fan, J. S., Roberts, R. T., Odorizzi, G. & Emr, S. D. (2024). A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting. Journal of Cell Biology, 223(4), e202307094-. https://dx.doi.org/10.1083/jcb.202307094 0021-9525 https://hdl.handle.net/10356/175617 10.1083/jcb.202307094 38319250 2-s2.0-85184456549 4 223 e202307094 en Journal of Cell Biology © 2024 Suzuki et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). application/pdf
spellingShingle Medicine, Health and Life Sciences
Endocytosis
Endosome
Suzuki, Sho W.
West, Matthew
Zhang, Yichen
Fan, Jenny S.
Roberts, Rachel T.
Odorizzi, Greg
Emr, Scott D.
A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting
title A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting
title_full A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting
title_fullStr A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting
title_full_unstemmed A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting
title_short A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting
title_sort role for vps13 mediated lipid transfer at the er endosome contact site in escrt mediated sorting
topic Medicine, Health and Life Sciences
Endocytosis
Endosome
url https://hdl.handle.net/10356/175617
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