PXD063770

PXD063770 is an original dataset announced via ProteomeXchange.

Title	Lymphangiogenesis by Relieving Caveolae-Mediated Inhibition of VEGFR3 Signaling
Description	The lymphatic system maintains tissue fluid balance, and its dysfunction can result in lymphedema. Although cholesterol is essential for cellular function, its role in lymphatic development has remained unknown. Here, we identify APOA1 binding protein (AIBP) as a key regulator that promotes lymphatic endothelial cell (LEC) fate specification and lymphangiogenesis. Mechanistically, AIBP reduces plasma membrane cholesterol content, thereby enhancing VEGFR3 signaling by disrupting caveolae—small plasma membrane invaginations formed by the scaffolding protein caveolin-1 (CAV-1)—and relieving CAV-1–mediated inhibition. In zebrafish and mice, AIBP loss impairs VEGFR3 signaling and lymphatic development, defects that can be rescued by CAV-1 deletion or by a VEGFR3 mutant (VEGFR3AAA) lacking CAV-1 binding. Administration of recombinant AIBP augments VEGFC-induced lymphangiogenesis and accelerates the resolution of secondary lymphedema in adult mice. These findings define the AIBP–CAV-1 axis as a critical regulator of VEGFR3 signaling and lymphatic growth, offering new therapeutic opportunities for treating lymphatic dysfunction.
HostingRepository	PRIDE
AnnounceDate	2025-10-27
AnnouncementXML	Submission_2025-10-26_17:53:03.521.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Longhou Fang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-08 09:30:51	ID requested
⏵ 1	2025-10-26 17:53:04	announced

10.1038/s41467-025-60611-w;

Kim JD, Chaudhary S, Chen W, Astin J, Crosier PS, Yu P, Cooke JP, Pownall HJ, Bellen HJ, Le NT, Kiss DL, Wang G, Rockson SG, Chen H, Fang L, APOA1 binding protein promotes lymphatic cell fate and lymphangiogenesis by relieving caveolae-mediated inhibition of VEGFR3 signaling. Nat Commun, 16(1):9286(2025) [pubmed]

submitter keyword: Caveolae,AIBP, Lymphangiogenesis, VEGFR3

Longhou Fang
contact affiliation	1Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute. Houston Methodist, 6550 Fannin Street, Texas 77030, USA.
contact email	lhfang@houstonmethodist.org
lab head
Longhou Fang
contact affiliation	Houston Methodist Research Institute
contact email	lhfang@houstonmethodist.org
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/2025/10/PXD063770

PRIDE project URI

• PRIDE
  1. PXD063770
     1. Label: PRIDE project
     2. Name: Lymphangiogenesis by Relieving Caveolae-Mediated Inhibition of VEGFR3 Signaling