Journal article
A Family of Tetraspans Organizes Cargo for Sorting into Multivesicular Bodies
Developmental cell, Vol.33(3), pp.328-342
05/04/2015
DOI: 10.1016/j.devcel.2015.03.007
PMCID: PMC4421094
PMID: 25942624
Abstract
The abundance of cell-surface membrane proteins is regulated by internalization and delivery into intralumenal vesicles (ILVs) of multivesicular bodies (MVBs). Many cargoes are ubiquitinated, allowing access to an ESCRT-dependent pathway into MVBs. Yet how nonubiquitinated proteins, such as glycosyl-phosphatidylinositol-anchored proteins, enter MVBs is unclear, supporting the possibility of mechanistically distinct ILV biogenesis pathways. Here we show that a family of highly ubiquitinated tetraspan Cos proteins provides a Ub signal in trans, allowing sorting of nonubiquitinated MVB cargo into the canonical ESCRT- and Ub-dependent pathway. Cos proteins create discrete endosomal subdomains that concentrate Ub cargo prior to their envelopment into ILVs, and the activity of Cos proteins is required not only for efficient sorting of canonical Ub cargo but also for sorting nonubiquitinated cargo into MVBs. Expression of these proteins increases during nutrient stress through an NAD(+)/Sir2-dependent mechanism that in turn accelerates the downregulation of a broad range of cell-surface proteins.
Details
- Title: Subtitle
- A Family of Tetraspans Organizes Cargo for Sorting into Multivesicular Bodies
- Creators
- Chris MacDonald - University of IowaJohanna A. Payne - Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA.Mariam Aboian - Mayo ClinicWilliam Smith - University of IowaDavid J. Katzmann - Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA.Robert C. Piper - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Developmental cell, Vol.33(3), pp.328-342
- Publisher
- Elsevier
- DOI
- 10.1016/j.devcel.2015.03.007
- PMID
- 25942624
- PMCID
- PMC4421094
- ISSN
- 1534-5807
- eISSN
- 1878-1551
- Number of pages
- 15
- Grant note
- R01-GM058202; R01-GM073024 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30CA086862 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) AHA; American Heart Association R01GM073024 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Language
- English
- Date published
- 05/04/2015
- Academic Unit
- Molecular Physiology and Biophysics; Medicine Administration; Internal Medicine
- Record Identifier
- 9984297599002771
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