PXD006416-1

PXD006416 is an original dataset announced via ProteomeXchange.

Title	Plasma membrane-derived extracellular microvesicles mediate non-canonical intercellular NOTCH signaling
Description	ARMMs (arrestin domain-containing protein 1 [ARRDC1]-mediated microvesicles) are extracellular vesicles that bud directly atthe plasma membrane. However, little is known about the physiological function of these vesicles. Here we report that secreted ARMMs contain active NOTCH receptors and mediate a non-canonical intercellular NOTCH signaling. Masss pectrometry of purified ARMMs identifiedNOTCH2 as a protein component of the vesicles. The NOTCH protein in ARMMs contains the critical intracellular region (NICD) that is required for its transcriptional activity in the nucleus. ARRDC1 overexpression increased the NOTCH2 incorporation into ARMMs. Conversely, CRISPR-mediated knockout of ARRDC1 dramatically reduced the amount of NOTCH2 in secreted ARMMs. The incorporation of NOTCH2 into ARMMs is facilitated by the ITCH E3 ligase and ADAM10, which are also secreted into ARMMs. We showed NOTCH2 in ARMMs delivered into recipient cells is further activated by γ-secretase cleavage to induce NOTCH-specific signaling in recipient cells. Together, our findings revealed a role for ARMMs in a novelNOTCH signaling pathway that acts in distance beyond direct cell-cell contact.
HostingRepository	PRIDE
AnnounceDate	2017-10-11
AnnouncementXML	Submission_2017-10-10_23:47:56.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Qiyu Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2017-05-02 01:30:09	ID requested
⏵ 1	2017-10-10 23:47:58	announced
2	2024-10-22 04:36:56	announced	2024-10-22: Updated project metadata.

Wang Q, Lu Q, Plasma membrane-derived extracellular microvesicles mediate non-canonical intercellular NOTCH signaling. Nat Commun, 8(1):709(2017) [pubmed]

curator keyword: Biological

submitter keyword: NOTCH, ARRDC1, ARMMs

Quan Lu
contact affiliation	Program in Molecular and Integrative Physiological Sciences, Departments of Environment Health and Genetics & Complex Diseases, T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA
contact email	qlu@hsph.harvard.edu
lab head
Qiyu Wang
contact affiliation	Harvard University
contact email	qiwang@hsph.harvard.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD006416

PRIDE project URI

• PRIDE
  1. PXD006416
     1. Label: PRIDE project
     2. Name: Plasma membrane-derived extracellular microvesicles mediate non-canonical intercellular NOTCH signaling