Cerebral cavernous malformation proteins at a glance

J Cell Sci. 2014 Feb 15;127(Pt 4):701-7. doi: 10.1242/jcs.138388. Epub 2014 Jan 30.

Abstract

Loss-of-function mutations in genes encoding KRIT1 (also known as CCM1), CCM2 (also known as OSM and malcavernin) or PDCD10 (also known as CCM3) cause cerebral cavernous malformations (CCMs). These abnormalities are characterized by dilated leaky blood vessels, especially in the neurovasculature, that result in increased risk of stroke, focal neurological defects and seizures. The three CCM proteins can exist in a trimeric complex, and each of these essential multi-domain adaptor proteins also interacts with a range of signaling, cytoskeletal and adaptor proteins, presumably accounting for their roles in a range of basic cellular processes including cell adhesion, migration, polarity and apoptosis. In this Cell Science at a Glance article and the accompanying poster, we provide an overview of current models of CCM protein function focusing on how known protein-protein interactions might contribute to cellular phenotypes and highlighting gaps in our current understanding.

Keywords: CCM; Cell signaling; Cerebral cavernous malformations; KRIT1; PCDC10; Rho Signaling; Vascular biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Capillary Permeability
  • Carrier Proteins / metabolism
  • Central Nervous System Neoplasms / blood supply
  • Central Nervous System Neoplasms / metabolism*
  • Hemangioma, Cavernous, Central Nervous System / blood supply
  • Hemangioma, Cavernous, Central Nervous System / metabolism*
  • Humans
  • KRIT1 Protein
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Neoplasm Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Signal Transduction
  • rho GTP-Binding Proteins / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • CCM2 protein, human
  • Carrier Proteins
  • KRIT1 Protein
  • KRIT1 protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • PDCD10 protein, human
  • Proto-Oncogene Proteins
  • rho GTP-Binding Proteins