QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 8 May 2007
doi: 10.1242/jcs.000703

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.000703v1 120/11/1859    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Berto, G. Articles by Di Cunto, F. Search for Related Content PubMed PubMed Citation Articles by Berto, G. Articles by Di Cunto, F. Social Bookmarking                         What's this?

The Down syndrome critical region protein TTC3 inhibits neuronal differentiation via RhoA and Citron kinase

¹ Molecular Biotechnology Center, Department of Genetics, Biology and Biochemistry, University of Turin, Italy
² Division of Experimental Pathology, Institute of Pathology, University of Lausanne, Lausanne, Switzerland
³ Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Cambridge, UK
⁴ Center for Experimental Research and Medical Studies and Department of Biomedical Sciences and Human Oncology, University of Turin, Italy

^* Author for correspondence (e-mail: ferdinando.dicunto{at}unito.it)

Accepted 11 April 2007

The Down syndrome critical region (DSCR) on Chromosome 21 contains many genes whose duplication may lead to the major phenotypic features of Down syndrome and especially the associated mental retardation. However, the functions of DSCR genes are mostly unknown and their possible involvement in key brain developmental events still largely unexplored. In this report we show that the protein TTC3, encoded by one of the main DSCR candidate genes, physically interacts with Citron kinase (CIT-K) and Citron N (CIT-N), two effectors of the RhoA small GTPase that have previously been involved in neuronal proliferation and differentiation. More importantly, we found that TTC3 levels can strongly affect the NGF-induced differentiation of PC12 cells, by a CIT-K-dependent mechanism. Indeed, TTC3 overexpression leads to strong inhibition of neurite extension, which can be reverted by CIT-K RNAi. Conversely, TTC3 knockdown stimulates neurite extension in the same cells. Finally, we find that Rho, but not Rho kinase, is required for TTC3 differentiation-inhibiting activity. Our results suggest that the TTC3–RhoA–CIT-K pathway could be a crucial determinant of in vivo neuronal development, whose hyperactivity may result in detrimental effects on the normal differentiation program.

Key words: Citron kinase, Neuronal differentiation, Rho, TTC3

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

A new Rho to Down syndrome

JCS 2007 120: 1101. [Full Text]  

This article has been cited by other articles:

				D. L. Ford-Speelman, J. A. Roche, A. L. Bowman, and R. J. Bloch The Rho-Guanine Nucleotide Exchange Factor Domain of Obscurin Activates RhoA Signaling in Skeletal Muscle Mol. Biol. Cell, September 1, 2009; 20(17): 3905 - 3917. [Abstract] [Full Text] [PDF]

				S. J. Sweeney, P. Campbell, and G. Bosco Drosophila sticky/citron kinase Is a Regulator of Cell-Cycle Progression, Genetically Interacts With Argonaute 1 and Modulates Epigenetic Gene Silencing Genetics, March 1, 2008; 178(3): 1311 - 1325. [Abstract] [Full Text] [PDF]