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Tetraspanin-enriched Membrane Domains Regulate Vascular Leakage by Membrane Cholesterol Accessibility to Balance Antagonistic GTPases.

ABSTRACT: As an endothelium destabilizer, CD82 facilitates vascular leakage by disrupting endothelial barrier and inhibiting its recovery during inflammation. AC at EC surface primes and promotes vascular leakage, mediates the effect of CD82 or TEMD on inflammation, and can be regulated specifically by i) tetraspanins or TEMDs, ii) ORP-mediated transfer of cholesterol, iii) environmental cholesterol, and iv) statin. Thus, tetraspanin-AC interaction and subcellular cholesterol compartmentalization tune the balances between antagonistic signaling axes of Cdc42 versus RhoA, to alter vascular leakage in inflammation. Equally important, we demonstrated anti-vascular leakage and anti-inflammation roles of i) AC reduction and ii) FARP1-Cdc42 elevation/activation in animal models, with promising translational and clinical prospects.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Zhiping Wu

LAB HEAD: Junmin Peng

PROVIDER: PXD065001 | Pride | 2025-06-19

REPOSITORIES: Pride

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			Action	DRS
	PRIDE_release_samplelist_v01.txt	Txt
	PRIDE_release_v01.docx	Other
	checksum.txt	Txt
	f01.1.pepXML	Pepxml
	f01.raw	Raw

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