Dynamic regulation of the cerebral cavernous malformation pathway controls vascular stability and growth. Academic Article uri icon

Overview

abstract

  • Cardiovascular growth must balance stabilizing signals required to maintain endothelial connections and network integrity with destabilizing signals that enable individual endothelial cells to migrate and proliferate. The cerebral cavernous malformation (CCM) signaling pathway utilizes the adaptor protein CCM2 to strengthen endothelial cell junctions and stabilize vessels. Here we identify a CCM2 paralog, CCM2L, that is expressed selectively in endothelial cells during periods of active cardiovascular growth. CCM2L competitively blocks CCM2-mediated stabilizing signals biochemically, in cultured endothelial cells, and in developing mice. Loss of CCM2L reduces endocardial growth factor expression and impairs tumor growth and wound healing. Our studies identify CCM2L as a molecular mechanism by which endothelial cells coordinately regulate vessel stability and growth during cardiovascular development, as well as postnatal vessel growth.

publication date

  • August 14, 2012

Research

keywords

  • Central Nervous System Vascular Malformations
  • Microfilament Proteins
  • Microtubule-Associated Proteins
  • Neovascularization, Pathologic

Identity

PubMed Central ID

  • PMC3743537

Scopus Document Identifier

  • 84865085052

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2012.06.004

PubMed ID

  • 22898778

Additional Document Info

volume

  • 23

issue

  • 2