PXD026618

PXD026618 is an original dataset announced via ProteomeXchange.

Title	βIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling
Description	Defective angiogenesis underlies over 50 malignant, ischemic and inflammatory disorders yet long-term therapeutic applications inevitably fail, thus highlighting the need for greater understanding of the vast crosstalk and compensatory mechanisms. Based on proteomic profiling of angiogenic endothelial components, here we report βIV-spectrin, a non-erythrocytic cytoskeletal protein, as a critical regulator of sprouting angiogenesis. Early loss of endothelial specific βIV-spectrin promotes embryonic lethality in mice due to hypervascularization and hemorrhagic defects whereas neonatal depletion yields higher vascular density and tip cell populations in developing retina. During sprouting, βIV-spectrin expresses in stalk cells to inhibit their tip cell potential by enhancing VEGFR2 turnover in a manner independent of most cell-fate determining mechanisms. Rather, βIV-spectrin recruits CaMKII to the plasma membrane to directly phosphorylate VEGFR2 at Ser984, a previously undefined phosphoregulatory site that strongly induces VEGFR2 internalization and degradation. These findings support a distinct spectrin-based mechanism of tip-stalk cell specification during vascular development.
HostingRepository	PRIDE
AnnounceDate	2022-02-04
AnnouncementXML	Submission_2022-02-04_01:29:11.957.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD026618
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Paul Langlais
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-10 07:54:25	ID requested
⏵ 1	2022-02-04 01:29:12	announced

Dataset with its publication pending

submitter keyword: Sprouting angiogenesis

VEGF signaling

tip-stalk cell specification

spectrins

Nam Lee
contact affiliation	University of Arizona College of Medicine-Tucson
contact email	namlee@arizona.edu
lab head
Paul Langlais
contact affiliation	University of Arizona
contact email	langlais@deptofmed.arizona.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026618
     1. Label: PRIDE project
     2. Name: βIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling