NDLI: Endolysosomal sorting of ubiquitinated caveolin-1 is regulated by VCP/p97 and UBXD1 and impaired by VCP disease mutations

Content Provider	PubMed Central
Author	Ritz, Danilo Vuk, Maja Kirchner, Philipp Monika, Bug Schütz, Sabina Hayer, Arnold Bremer, Sebastian Lusk, Caleb Baloh, Robert H. Lee, Houkeun Glatter, Timo Matthias, Gstaiger Aebersold, Ruedi Weihl, Conrad C. Meyer, Hemmo
Abstract	The AAA-ATPase VCP/p97 cooperates with distinct cofactors to process ubiquitinated proteins in different cellular pathways 1–3 . VCP missense mutations cause a systemic degenerative disease in humans, but the molecular pathogenesis is unclear 4, 5 . We used an unbiased mass spectrometry approach and identified a VCP complex with the UBXD1 cofactor, which binds the plasma membrane protein caveolin-1 (Cav1) and whose formation is specifically disrupted by disease-associated mutations. We show that VCP-UBXD1 targets mono-ubiquitinated Cav1 in SDS-resistant high molecular weight complexes on endosomes, which are en route to degradation in endolysosomes 6 . Expression of VCP mutant proteins, chemical inhibition of VCP, or siRNA-mediated depletion of UBXD1 leads to a block of Cav1 transport at the limiting membrane of enlarged endosomes in cultured cells. In patient muscle, muscle-specific Caveolin-3 (Cav3) accumulates in sarcoplasmic pools and specifically delocalises from the sarcolemma. These results extend the cellular functions of VCP to mediating sorting of ubiquitinated cargo in the endocytic pathway and suggest that impaired trafficking of caveolin may contribute to the pathogenesis in individuals with VCP mutations.
Related Links	http://dx.doi.org/10.1038/ncb2301
Ending Page	1123
Page Count	8
Starting Page	1116
File Format	PDF
ISSN	14657392
e-ISSN	14764679
Journal	Nature cell biology
Issue Number	9
Volume Number	13
Language	English
Publisher Date	2011-08-01
Access Restriction	Open
Subject Keyword	Cell Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Ubiquitination of the N-terminal Region of Caveolin-1 Regulates Endosomal Sorting by the VCP/p97 AAA-ATPase*

Ubiquitination of the N-terminal Region of Caveolin-1 Regulates Endosomal Sorting by the VCP/p97 AAA-ATPase

VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD

UBXD1 is a mitochondrial recruitment factor for p97/VCP and promotes mitophagy

Ubiquitination of the N-terminal Region of Caveolin-1 Regulates Endosomal Sorting by the VCP/p97 $AAA-ATPase^{*}$

Localized K63 ubiquitin signaling is regulated by VCP/p97 during oxidative stress

Caveolin-1 is ubiquitinated and targeted to intralumenal vesicles in endolysosomes for degradation

Impaired Protein Aggregate Handling and Clearance Underlie the Pathogenesis of p97/VCP-associated Disease*

Hereditary Inclusion Body Myopathy-Linked p97/VCP Mutations in the NH2 Domain and the D1 Ring Modulate p97/VCP ATPase Activity and D2 Ring Conformation▿

Endolysosomal sorting of ubiquitinated caveolin-1 is regulated by VCP/p97 and UBXD1 and impaired by VCP disease mutations

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Ubiquitination of the N-terminal Region of Caveolin-1 Regulates Endosomal Sorting by the VCP/p97 AAA-ATPase*

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Endolysosomal sorting of ubiquitinated caveolin-1 is regulated by VCP/p97 and UBXD1 and impaired by VCP disease mutations