التفاصيل البيبلوغرافية
| العنوان: |
A Collapsin Response Mediator Protein 2 Isoform Controls Myosin II-Mediated Cell Migration and Matrix Assembly by Trapping ROCK II. |
| المؤلفون: |
Yoneda, Atsuko, Morgan-Fisher, Marie, Wait, Robin, Couchman, John R., Wewer, Ulla M. |
| المصدر: |
Molecular & Cellular Biology; May2012, Vol. 32 Issue 10, p1788-1804, 17p |
| مصطلحات موضوعية: |
COLLAPSINS, MYOSIN, CELL migration, CANCER cells, EPITHELIAL cells |
| مستخلص: |
Collapsin response mediator protein 2 (CRMP-2) is known as a regulator of neuronal polarity and differentiation through microtubule assembly and trafficking. Here, we show that CRMP-2 is ubiquitously expressed and a splice variant (CRMP-2L), which is expressed mainly in epithelial cells among nonneuronal cells, regulates myosin II-mediated cellular functions, including cell migration. While the CRMP-2 short form (CRMP-2S) is recognized as a substrate of the Rho-GTP downstream kinase ROCK in neuronal cells, a CRMP-2 complex containing 2L not only bound the catalytic domain of ROCK II through two binding domains but also trapped and inhibited the kinase. CRMP-2L protein levels profoundly affected haptotactic migration and the actin-myosin cytoskeleton of carcinoma cells as well as nontransformed epithelial cell migration in a ROCK activity-dependent manner. Moreover, the ectopic expression of CRMP-2L but not -2S inhibited fibronectin matrix assembly in fibroblasts. Underlying these responses, CRMP-2L regulated the kinase activity of ROCK II but not ROCK I, independent of GTP-RhoA levels. This study provides a new insight into CRMP-2 as a controller of myosin II - mediated cellular functions through the inhibition of ROCK II in nonneuronal cells. [ABSTRACT FROM AUTHOR] |
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