Signaling pathways and the cerebral cavernous malformations proteins: lessons from structural biology.
Cell Mol Life Sci
; 71(10): 1881-92, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24287896
ABSTRACT
Cerebral cavernous malformations (CCM) are neurovascular dysplasias that result in mulberry-shaped lesions predominantly located in brain and spinal tissues. Mutations in three genes are associated with CCM. These genes encode for the proteins KRIT1/CCM1 (krev interaction trapped 1/cerebral cavernous malformations 1), cerebral cavernous malformations 2, osmosensing scaffold for MEKK3 (CCM2/malcavernin/OSM), and cerebral cavernous malformations 3/programmed cell death 10 (CCM3/PDCD10). There have been many significant recent advances in our understanding of the structure and function of these proteins, as well as in their roles in cellular signaling. Here, we provide an update on the current knowledge of the structure of the CCM proteins and their functions within cellular signaling, particularly in cellular adhesion complexes and signaling cascades. We go on to discuss subcellular localization of the CCM proteins, the formation and regulation of the CCM complex signaling platform, and current progress towards targeted therapy for CCM disease. Recent structural studies have begun to shed new light on CCM protein function, and we focus here on how these studies have helped inform the current understanding of these roles and how they may aid future studies into both CCM-related biology and disease mechanisms.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteínas de Transporte
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Proteínas de Membrana
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Proteínas Associadas aos Microtúbulos
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article