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

J. Biol. Chem., Vol. 278, Issue 27, 25024-25031, July 4, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/27/25024    most recent M303084200v1 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Buhusi, M. Articles by Maness, P. F. Search for Related Content PubMed PubMed Citation Articles by Buhusi, M. Articles by Maness, P. F. Social Bookmarking                      What's this?

Close Homolog of L1 Is an Enhancer of Integrin-mediated Cell Migration^*

Mona Buhusi  , Bentley R. Midkiff , Amanda M. Gates , Melanie Richter ¶, Melitta Schachner ¶ and Patricia F. Maness  ||

From the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260 and the ^¶Universitätsklinik Hamburg Eppendorf, Zentrum für Molekulare Neurobiologie, Institut für Biosynthese Neuraler Strukturen, D-20246 Hamburg, Germany

Close homolog of L1 (CHL1) is a member of the L1 family of cell adhesion molecules expressed by subpopulations of neurons and glia in the central and peripheral nervous system. It promotes neurite outgrowth and neuronal survival in vitro. This study describes a novel function for CHL1 in potentiating integrin-dependent cell migration toward extracellular matrix proteins. Expression of CHL1 in HEK293 cells stimulated their haptotactic migration toward collagen I, fibronectin, laminin, and vitronectin substrates in Transwell assays. CHL1-potentiated cell migration to collagen I was dependent on ₁₁ and ₂₁ integrins, as shown with function blocking antibodies. Potentiated migration relied on the early integrin signaling intermediates c-Src, phosphatidylinositol 3-kinase, and mitogen-activated protein kinase. Enhancement of migration was disrupted by mutation of a potential integrin interaction motif Asp-Gly-Glu-Ala (DGEA) in the sixth immunoglobulin domain of CHL1, suggesting that CHL1 functionally interacts with ₁ integrins through this domain. CHL1 was shown to associate with ₁ integrins on the cell surface by antibody-induced co-capping. Through a cytoplasmic domain sequence containing a conserved tyrosine residue (Phe-Ile-Gly-Ala-Tyr), CHL1 recruited the actin cytoskeletal adapter protein ankyrin to the plasma membrane, and this sequence was necessary for promoting integrin-dependent migration to extracellular matrix proteins. These results support a role for CHL1 in integrin-dependent cell migration that may be physiologically important in regulating cell migration in nerve regeneration and cortical development.

Received for publication, March 25, 2003 , and in revised form, April 24, 2003.

^* This work was supported by National Institutes of Health Grants NS26620 and MH064056 (to the University of North Carolina NIMH Silvio Conte Center for Neuroscience of Mental Disorders). 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.

Helen Lyng White Fellow in Neuroscience.

^|| To whom correspondence should be addressed: Dept. of Biochemistry and Biophysics, 505 Mary Ellen Jones Bldg., CB#7260, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7260. Tel.: 919-966-2323; Fax: 919-966-2852; E-mail: srclab{at}med.unc.edu.

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

This article has been cited by other articles:

				I. Jakovcevski, J. Wu, N. Karl, I. Leshchyns'ka, V. Sytnyk, J. Chen, A. Irintchev, and M. Schachner Glial Scar Expression of CHL1, the Close Homolog of the Adhesion Molecule L1, Limits Recovery after Spinal Cord Injury J. Neurosci., July 4, 2007; 27(27): 7222 - 7233. [Abstract] [Full Text] [PDF]

				M. F. McManus and J. A. Golden Topical Review: Neuronal Migration in Developmental Disorders J Child Neurol, April 1, 2005; 20(4): 280 - 286. [Abstract] [PDF]

				V. Bodrikov, I. Leshchyns'ka, V. Sytnyk, J. Overvoorde, J. den Hertog, and M. Schachner RPTP{alpha} is essential for NCAM-mediated p59fyn activation and neurite elongation J. Cell Biol., January 3, 2005; 168(1): 127 - 139. [Abstract] [Full Text] [PDF]

				V. E. Mick, T. K. Starr, T. M. McCaughtry, L. K. McNeil, and K. A. Hogquist The Regulated Expression of a Diverse Set of Genes during Thymocyte Positive Selection In Vivo J. Immunol., November 1, 2004; 173(9): 5434 - 5444. [Abstract] [Full Text] [PDF]

				H. Muramatsu, P. Zou, H. Suzuki, Y. Oda, G.-Y. Chen, N. Sakaguchi, S. Sakuma, N. Maeda, M. Noda, Y. Takada, et al. {alpha}4{beta}1- and {alpha}6{beta}1-integrins are functional receptors for midkine, a heparin-binding growth factor J. Cell Sci., October 15, 2004; 117(22): 5405 - 5415. [Abstract] [Full Text] [PDF]

				U. Gurok, C. Steinhoff, B. Lipkowitz, H.-H. Ropers, C. Scharff, and U. A. Nuber Gene Expression Changes in the Course of Neural Progenitor Cell Differentiation J. Neurosci., June 30, 2004; 24(26): 5982 - 6002. [Abstract] [Full Text] [PDF]

				S. Naus, M. Richter, D. Wildeboer, M. Moss, M. Schachner, and J. W. Bartsch Ectodomain Shedding of the Neural Recognition Molecule CHL1 by the Metalloprotease-disintegrin ADAM8 Promotes Neurite Outgrowth and Suppresses Neuronal Cell Death J. Biol. Chem., April 16, 2004; 279(16): 16083 - 16090. [Abstract] [Full Text] [PDF]

				M. F. McManus and J. A. Golden Topical Review: Neuronal Migration in Developmental Disorders J Child Neurol, March 1, 2004; 19(3): 280 - 286. [Abstract] [PDF]