Concepts and hypothesis: integrin cytoplasmic domain-associated protein-1 (ICAP-1) as a potential player in cerebral cavernous malformation.
Cerebral cavernous malformation (CCM) is a common vascular disease in central nervous system that frequently predisposes to stroke, seizure, and cerebral hemorrhage. CCM lesions are characterized by dilated and leaky intracranial capillaries composed of a thin layer of vascular endothelial cells with abnormal subendothelial extracellular matrix. Despite the understanding that genetic mutation of three CCM genes (CCM1, CCM2, and CCM3) results in hereditary CCM, the molecular mechanism underlying vascular defects in CCM lesions remains poorly understood. Recent studies have shown that integrin cytoplasmic domain-associated protein-1 (ICAP-1, also known as integrin β1 binding protein1, ITGB1BP), a cytoplasmic protein interacting with both β1 integrin subunit and CCM1 protein (also known as Krit1), is implicated in vascular development. Analysis of data on the biochemistry and cellular biology of ICAP-1 highlights that bidirectional interaction of ICAP-1 with CCM1 and integrin might regulate diverse pathological processes of CCM disorder. Specifically, emerging evidence supports the hypothesized involvement of ICAP-1 in CCM pathogenesis through its significant effect in attenuating excessive vascular growth, its indispensable function in activating CCM1 protein, and its essential role in regulating integrin functions.
Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Chongqing Engineering Laboratory in Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, People's Republic of China.
Yiming
Y
Zheng
Juhui
J
Qiu
Jianjun
J
Hu
Guixue
G
Wang
D048868:Adaptor Proteins, Signal Transducing; D002319:Cardiovascular System / Q000378:metabolism / Q000473:pathology; D020786:Hemangioma, Cavernous, Central Nervous System / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C108257:ITGB1BP1 protein, human; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins