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

J. Biol. Chem., Vol. 282, Issue 18, 13692-13702, May 4, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/18/13692    most recent M610873200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Endo, M. Articles by Mizuno, K. Search for Related Content PubMed PubMed Citation Articles by Endo, M. Articles by Mizuno, K. Social Bookmarking                      What's this?

LIM Kinase and Slingshot Are Critical for Neurite Extension^*

From the Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan

Cofilin and its closely related protein, actin-depolymerizing factor (ADF), are key regulators of actin cytoskeleton dynamics that have been implicated in growth cone motility and neurite extension. Cofilin/ADF are inactivated by LIM kinase (LIMK)-catalyzed phosphorylation and reactivated by Slingshot (SSH)-catalyzed dephosphorylation. Here we examined the roles of cofilin/ADF, LIMKs (LIMK1 and LIMK2), and SSHs (SSH1 and SSH2) in nerve growth factor (NGF)-induced neurite extension. Knockdown of cofilin/ADF by RNA interference almost completely inhibited NGF-induced neurite extension from PC12 cells, and double knockdown of SSH1/SSH2 significantly suppressed both NGF-induced cofilin/ADF dephosphorylation and neurite extension from PC12 cells, thus indicating that cofilin/ADF and their activating phosphatases SSH1/SSH2 are critical for neurite extension. Interestingly, NGF stimulated the activities of both LIMK1 and LIMK2 in PC12 cells, and suppression of LIMK1/LIMK2 expression or activity significantly reduced NGF-induced neurite extension from PC12 cells or chick dorsal root ganglion (DRG) neurons. Inhibition of LIMK1/LIMK2 activity reduced actin filament assembly in the peripheral region of the growth cone of chick DRG neurons. These results suggest that proper regulation of cofilin/ADF activities through control of phosphorylation by LIMKs and SSHs is critical for neurite extension and that LIMKs regulate actin filament assembly at the tip of the growth cone.

Received for publication, November 27, 2006 , and in revised form, February 5, 2007.

^* This work was supported by a grant-in aid for scientific research from the Ministry of Education, Culture, Science, Sports and Technology of Japan. 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S7.

¹ To whom correspondence should be addressed. Tel.: 81-22-795-6676; Fax: 81-22-795-6678; E-mail: kmizuno{at}biology.tohoku.ac.jp.

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

This article has been cited by other articles:

				Y. Hasegawa, G. D. Tribble, H. V. Baker, J. J. Mans, M. Handfield, and R. J. Lamont Role of Porphyromonas gingivalis SerB in Gingival Epithelial Cell Cytoskeletal Remodeling and Cytokine Production Infect. Immun., June 1, 2008; 76(6): 2420 - 2427. [Abstract] [Full Text] [PDF]

				A. I. Ivanov, A. M. Hopkins, G. T. Brown, K. Gerner-Smidt, B. A. Babbin, C. A. Parkos, and A. Nusrat Myosin II regulates the shape of three-dimensional intestinal epithelial cysts J. Cell Sci., June 1, 2008; 121(11): 1803 - 1814. [Abstract] [Full Text] [PDF]

				Y. Horita, K. Ohashi, M. Mukai, M. Inoue, and K. Mizuno Suppression of the Invasive Capacity of Rat Ascites Hepatoma Cells by Knockdown of Slingshot or LIM Kinase J. Biol. Chem., March 7, 2008; 283(10): 6013 - 6021. [Abstract] [Full Text] [PDF]

				N. Kaji, A. Muramoto, and K. Mizuno LIM Kinase-mediated Cofilin Phosphorylation during Mitosis Is Required for Precise Spindle Positioning J. Biol. Chem., February 22, 2008; 283(8): 4983 - 4992. [Abstract] [Full Text] [PDF]

				S. Chandramouli, C. Y. Yu, P. Yusoff, D.-H. Lao, H. F. Leong, K. Mizuno, and G. R. Guy Tesk1 Interacts with Spry2 to Abrogate Its Inhibition of ERK Phosphorylation Downstream of Receptor Tyrosine Kinase Signaling J. Biol. Chem., January 18, 2008; 283(3): 1679 - 1691. [Abstract] [Full Text] [PDF]

				Z. Wen, L. Han, J. R. Bamburg, S. Shim, G.-l. Ming, and J. Q. Zheng BMP gradients steer nerve growth cones by a balancing act of LIM kinase and Slingshot phosphatase on ADF/cofilin J. Cell Biol., October 3, 2007; 178(1): 107 - 119. [Abstract] [Full Text] [PDF]