HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 27, 19884-19893, July 6, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/27/19884    most recent M700770200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mori, T. Articles by Inagaki, N. Search for Related Content PubMed PubMed Citation Articles by Mori, T. Articles by Inagaki, N. Related Collections Papers Of The Week Social Bookmarking                      What's this?

Singar1, a Novel RUN Domain-containing Protein, Suppresses Formation of Surplus Axons for Neuronal Polarity^*

Tatsuya Mori, Tomoe Wada, Takahiro Suzuki, Yoshitsugu Kubota, and Naoyuki Inagaki¹

From the Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630-0192 and the Department of Transfusion Medicine, Faculty of Medicine, Kagawa University, Kagawa 760-0793, Japan

Although neuronal functions depend on their robust polarity, the mechanisms that ensure generation and maintenance of only a single axon remain poorly understood. Using highly sensitive two-dimensional electrophoresis-based proteomics, we identified here a novel protein, single axon-related (singar)1/KIAA0871/RPIPx/RUFY3, which contains a RUN domain and is predominantly expressed in the brain. Singar1 expression became up-regulated during polarization of cultured hippocampal neurons and remained at high levels thereafter. Singar1 was diffusely localized in hippocampal neurons and moderately accumulated in growth cones of minor processes and axons. Overexpression of singar1 did not affect normal neuronal polarization but suppressed the formation of surplus axons induced by excess levels of shootin1, a recently identified protein located upstream of phosphoinositide-3-kinase and involved in neuronal polarization. Conversely, reduction of the expression of singar1 and its splicing variant singar2 by RNA interference led to an increase in the population of neurons bearing surplus axons, in a phosphoinositide-3-kinase-dependent manner. Overexpression of singar2 did not suppress the formation of surplus axons induced by shootin1. We propose that singar1 ensures the robustness of neuronal polarity by suppressing formation of surplus axons.

Received for publication, January 26, 2007 , and in revised form, April 10, 2007.

^* This work was supported in part by Grants-in-Aid for Scientific Research on Priority Areas 18016020 and 18022028 from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Japan Society for the Promotion of Science KAKENHI (Grant 18300107), and a grant from the Osaka Medical Research Foundation for Incurable Diseases. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

This article was selected as a Paper of the Week.

The on-line version of this article (available at http://www.jbc.org) contains two supplemental figures.

¹ To whom correspondence should be addressed. Tel.: 81-743-72-5441; Fax: 81-743-72-5449; E-mail: ninagaki{at}bs.naist.jp.

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