β_IV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling.

ABSTRACT: 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 β_IV-spectrin, a non-erythrocytic cytoskeletal protein, as a critical regulator of sprouting angiogenesis. Early loss of endothelial-specific β_IV-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, β_IV-spectrin expresses in stalk cells to inhibit their tip cell potenti

SUBMITTER: Kwak EA 

PROVIDER: S-EPMC8921520 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature