MARCKS mediates vascular contractility through regulating interactions between voltage-gated Ca²⁺ channels and PIP₂.

ABSTRACT: Phosphatidylinositol 4,5-bisphosphate (PIP₂) acts as substrate and unmodified ligand for Gq-protein-coupled receptor signalling in vascular smooth muscle cells (VSMCs) that is central for initiating contractility. The present work investigated how PIP₂ might perform these two potentially conflicting roles by studying the effect of myristoylated alanine-rich C kinase substrate (MARCKS), a PIP₂-binding protein, on vascular contractility in rat and mouse mesenteric arteries. Using wire myography, MANS peptide (MANS), a MARCKS inhibitor, produced robust contractions with a pharmacological profile suggesting a predominantly role for L-type (CaV1.2) voltage-gated Ca²⁺ channels (VGCC). Knockdown of MARCKS using morpholino oligonucleotides reduced contra

SUBMITTER: Jahan KS 

PROVIDER: S-EPMC7549404 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature