Cerebral cavernous malformation proteins at a glance.
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.
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520-8066, USA.
Kyle M
KM
Draheim
Oriana S
OS
Fisher
Titus J
TJ
Boggon
David A
DA
Calderwood
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002199:Capillary Permeability; D002352:Carrier Proteins / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000098:blood supply / Q000378:metabolism*; D020786:Hemangioma, Cavernous, Central Nervous System / Q000098:blood supply / Q000378:metabolism*; D006801:Humans; D000075927:KRIT1 Protein; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C502544:CCM2 protein, human; D002352:Carrier Proteins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins; D020741:rho GTP-Binding Proteins
CCM; Cell signaling; Cerebral cavernous malformations; KRIT1; PCDC10; Rho Signaling; Vascular biology