TAILIEUCHUNG - Báo cáo khoa học: Recent insights into cerebral cavernous malformations: a complex jigsaw puzzle under construction

Cerebral cavernous malformations (CCM) are common vascular malforma-tions with an unpredictable risk of hemorrhage, the consequences of which range from headache to stroke or death. Three genes, CCM1, CCM2and CCM3, have been linked to the disease. The encoded CCM proteins inter-act with each other within a large protein complex. | MINIREVIEW Recent insights into cerebral cavernous malformations a complex jigsaw puzzle under construction Eva Faurobert and Corinne Albiges-Rizo Centre de recherche INSERM U823-CNRS ERL 3148 Universite J. Fourier Grenoble France Keywords angiogenesis blood brain barrier cadherin CCM cytoskeleton endothelial cell HEG hemorrhage integrin Krit1 Correspondence E. Faurobert Centre de recherche INSERM U823-CNRS ERL 3148 Universite J. Fourier Site sante La tronche BP170 38042 Grenoble France Fax 33 476 54 94 25 Tel 33 476 54 94 74 E-mail Received 1 August 2009 revised 4 November 2009 accepted 25 November 2009 doi Cerebral cavernous malformations CCM are common vascular malformations with an unpredictable risk of hemorrhage the consequences of which range from headache to stroke or death. Three genes CCM1 CCM2 and CCM3 have been linked to the disease. The encoded CCM proteins interact with each other within a large protein complex. Within the past 2 years a plethora of new data has emerged on the signaling pathways in which CCM proteins are involved. CCM proteins regulate diverse aspects of endothelial cell morphogenesis and blood vessel stability such as cell-cell junctions cell shape and polarity or cell adhesion to the extracellular matrix. Although fascinating a global picture is hard to depict because little is known about how these pathways coordinate to orchestrate angiogenesis. Here we present what is known about the structural domain organization of CCM proteins their association as a ternary complex and their subcellular localization. Numerous CCM partners have been identified using two-hybrid screens genetic analyses or proteomic studies. We focus on the best-characterized partners and review data on the signaling pathways they regulate as a step towards a better understanding of the etiology of CCM disease. Introduction Cerebral cavernous malformations CCM are common vascular malformations with a

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