Structural highlights
Disease
VINC_HUMAN Defects in VCL are the cause of cardiomyopathy dilated type 1W (CMD1W) [MIM:611407. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.[1] [2] Defects in VCL are the cause of familial hypertrophic cardiomyopathy type 15 (CMH15) [MIM:613255. It is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.[3]
Function
VINC_HUMAN Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion.[4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The translational machinery of the cell relocalizes to focal adhesions following the activation of integrin receptors. This response allows for rapid, local production of components needed for adhesion complex assembly and signaling. Vinculin links focal adhesions to the actin cytoskeleton following its activation by integrin signaling, which severs intramolecular interactions of vinculin's head and tail (Vt) domains. Our vinculin:raver1 crystal structures and binding studies show that activated Vt selectively interacts with one of the three RNA recognition motifs of raver1, that the vinculin:raver1 complex binds to F-actin, and that raver1 binds selectively to RNA, including a sequence found in vinculin mRNA. Further, mutation of residues that mediate interaction of raver1 with vinculin abolish their colocalization in cells. These findings suggest a feed-forward model where vinculin activation at focal adhesions provides a scaffold for recruitment of raver1 and its mRNA cargo to facilitate the production of components of adhesion complexes.
Raver1 interactions with vinculin and RNA suggest a feed-forward pathway in directing mRNA to focal adhesions.,Lee JH, Rangarajan ES, Yogesha SD, Izard T Structure. 2009 Jun 10;17(6):833-42. PMID:19523901[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Olson TM, Illenberger S, Kishimoto NY, Huttelmaier S, Keating MT, Jockusch BM. Metavinculin mutations alter actin interaction in dilated cardiomyopathy. Circulation. 2002 Jan 29;105(4):431-7. PMID:11815424
- ↑ Vasile VC, Will ML, Ommen SR, Edwards WD, Olson TM, Ackerman MJ. Identification of a metavinculin missense mutation, R975W, associated with both hypertrophic and dilated cardiomyopathy. Mol Genet Metab. 2006 Feb;87(2):169-74. Epub 2005 Oct 19. PMID:16236538 doi:S1096-7192(05)00258-1
- ↑ Vasile VC, Ommen SR, Edwards WD, Ackerman MJ. A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2006 Jul 7;345(3):998-1003. Epub 2006 May 4. PMID:16712796 doi:S0006-291X(06)00981-8
- ↑ Le Clainche C, Dwivedi SP, Didry D, Carlier MF. Vinculin is a dually regulated actin filament barbed end-capping and side-binding protein. J Biol Chem. 2010 Jul 23;285(30):23420-32. doi: 10.1074/jbc.M110.102830. Epub, 2010 May 18. PMID:20484056 doi:10.1074/jbc.M110.102830
- ↑ Lee JH, Rangarajan ES, Yogesha SD, Izard T. Raver1 interactions with vinculin and RNA suggest a feed-forward pathway in directing mRNA to focal adhesions. Structure. 2009 Jun 10;17(6):833-42. PMID:19523901 doi:S0969-2126(09)00193-2
