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The product of the ?-secretase processing of ephrinB2 regulates VE-cadherin complexes and angiogenesis.

ABSTRACT: Presenilin-1 (PS1) gene encodes the catalytic component of ?-secretase, which proteolytically processes several type I transmembrane proteins. We here present evidence that the cytosolic peptide efnB2/CTF2 produced by the PS1/?-secretase cleavage of efnB2 ligand promotes EphB4 receptor-dependent angiogenesis in vitro. EfnB2/CTF2 increases endothelial cell sprouting and tube formation, stimulates the formation of angiogenic complexes that include VE-cadherin, Raf-1 and Rok-?, and increases MLC2 phosphorylation. These functions are mediated by the PDZ-binding domain of efnB2. Acute downregulation of PS1 or inhibition of ?-secretase inhibits the angiogenic functions of EphB4 while absence of PS1 decreases the VE-cadherin angiogenic complexes of mouse brain. Our data reveal a mechanism by which PS1/?-secretase regulates efnB2/EphB4 mediated angiogenesis.

SUBMITTER: Warren NA

PROVIDER: S-EPMC6023733 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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The product of the γ-secretase processing of ephrinB2 regulates VE-cadherin complexes and angiogenesis.

Warren Noel A NA Voloudakis Georgios G Yoon Yonejung Y Robakis Nikolaos K NK Georgakopoulos Anastasios A

Cellular and molecular life sciences : CMLS 20180210 15

Presenilin-1 (PS1) gene encodes the catalytic component of γ-secretase, which proteolytically processes several type I transmembrane proteins. We here present evidence that the cytosolic peptide efnB2/CTF2 produced by the PS1/γ-secretase cleavage of efnB2 ligand promotes EphB4 receptor-dependent angiogenesis in vitro. EfnB2/CTF2 increases endothelial cell sprouting and tube formation, stimulates the formation of angiogenic complexes that include VE-cadherin, Raf-1 and Rok-α, and increases MLC2 p ...[more]

PMID: 29428965

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