First published online May 21, 2007
Journal of Cell Science 120, 1101e (2007)
© The Company of Biologists Limited
A new Rho to Down syndrome
Rho GTPases – master regulators of the actin cytoskeleton – help to control neuronal proliferation and differentiation during central nervous system development through interactions with a network of effector proteins. These include Citron-kinase (CIT-K) and Citron-N, two proteins encoded by the same gene. Now, Ferdinando Di Cunto and colleagues report that TTC3, the product of a gene on chromosome 21 that is duplicated in Down syndrome, interacts with CIT-K to control neuronal differentiation (see p. 1859). Having discovered the interaction between TTC3 and the Citron proteins in a two-hybrid screen, the authors show that TTC3 overexpression inhibits NGF-induced neurite extension in PC12 neuroblastoma cells and that knocking down CIT-K by RNAi alleviates this inhibition. Conversely, knocking down TTC3 stimulates neurite extension in PC12 cells. The authors also report that TTC3 expression increases the levels of active RhoA and that the inhibitory effects of TTC3 require RhoA. Thus, they suggest, a TTC3/RhoA/CIT-K pathway helps to control neuronal development and TTC3 gene duplication could contribute to mental retardation in Down syndrome.
Related articles in JCS:
- The Down syndrome critical region protein TTC3 inhibits neuronal differentiation via RhoA and Citron kinase
- Gaia Berto, Paola Camera, Carlo Fusco, Sara Imarisio, Chiara Ambrogio, Roberto Chiarle, Lorenzo Silengo, and Ferdinando Di Cunto
JCS 2007 120: 1859-1867.
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