PXD032903

PXD032903 is an original dataset announced via ProteomeXchange.

Title	VCP-dependent CNN2 proximity proteomics
Description	Lysosomal membrane permeabilization (LMP) is an underlying feature of diverse conditions including neurodegeneration. Cells respond by extensive ubiquitylation of membrane-associated proteins for clearance of the organelle through lysophagy that is facilitated by the ubiquitin-directed AAA-ATPase VCP/p97. Here, we assessed the ubiquitylated proteome upon acute LMP and uncovered a large diversity of targets and lysophagy regulators. They include calponin-2 (CNN2) that, along with the Arp2/3 complex, translocates to damaged lysosomes and regulates actin filaments to drive phagophore formation. Importantly, CNN2 needs to be ubiquitylated during the process and eliminated by VCP/p97 and proteasome for efficient lysophagy. Moreover, we identified the small heat shock protein HSPB1 that assists VCP/p97 in extraction of CNN2, and show that other membrane regulators including SNAREs, PICALM, AGFG1 and ARL8B are ubiquitylated during lysophagy. Our data reveal a framework of how ubiquitylation and two effectors, VCP/p97 and HSPB1, cooperate to protect cells from the deleterious effects of LMP.
HostingRepository	PRIDE
AnnounceDate	2022-06-23
AnnouncementXML	Submission_2022-06-23_04:01:29.317.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Behrends
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-02 10:32:24	ID requested
⏵ 1	2022-06-23 04:01:29	announced

Dataset with its publication pending

submitter keyword: CNN2, VCP, NMS873, APEX2

Christian Behrends
contact affiliation	SyNergy, LMU München
contact email	christian.behrends@mail03.med.uni-muenchen.de
lab head
Christian Behrends
contact affiliation	SyNergy, LMU München
contact email	christian.behrends@mail03.med.uni-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD032903
     1. Label: PRIDE project
     2. Name: VCP-dependent CNN2 proximity proteomics