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

J. Biol. Chem., Vol. 278, Issue 35, 32561-32568, August 29, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/35/32561    most recent M302943200v1 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 Geisbrecht, B. V. Articles by Leahy, D. J. Search for Related Content PubMed PubMed Citation Articles by Geisbrecht, B. V. Articles by Leahy, D. J. Social Bookmarking                      What's this?

Netrin Binds Discrete Subdomains of DCC and UNC5 and Mediates Interactions between DCC and Heparin^*

Brian V. Geisbrecht , Kimberly A. Dowd, Ronald W. Barfield, Patti A. Longo and Daniel J. Leahy 

From the Howard Hughes Medical Institute and the Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Netrins are secreted proteins that elicit both attractive and repulsive responses in migrating cells in the central and peripheral nervous systems. Netrins interact with members of two distinct families of transmembrane receptors, represented by DCC (deleted in colorectal cancer) and UNC5. A human netrin fragment (soluble netrin; sNetrin) was purified from an engineered Chinese hamster ovary cell line and used in a pull-down assay to map the interactions between netrin and its receptors. We find that sNetrin binds exclusively to the fifth fibronectin type III repeat of DCC and to each immunoglobulin repeat of UNC5. Both DCC and UNC5 bind to sNetrin with 1:1 stoichiometry in solution, and the minimal receptor fragments behave similarly to larger fragments in cross-linking experiments with purified sNetrin. We find no evidence for formation of a ternary complex between sNetrin and soluble forms of DCC and UNC5. We also find no evidence for an interaction between DCC and heparin and instead demonstrate that a loop on the fifth fibronectin type III repeat of DCC previously implicated in mediating interactions with heparin is important for sNetrin binding. Since netrin binds heparin, our results suggest that interactions between DCC and heparin are probably mediated by netrin.

Received for publication, March 21, 2003 , and in revised form, June 12, 2003.

^* 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.

Postdoctoral Fellow of the Howard Hughes Medical Institute.

An Assistant Investigator of the Howard Hughes Medical Institute. To whom correspondence should be addressed: Howard Hughes Medical Institute and Dept. of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205. Tel.: 410-614-2533; Fax: 410-614-8839; E-mail: dleahy{at}jhmi.edu.

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

This article has been cited by other articles:

				J. Fitamant, C. Guenebeaud, M.-M. Coissieux, C. Guix, I. Treilleux, J.-Y. Scoazec, T. Bachelot, A. Bernet, and P. Mehlen Netrin-1 expression confers a selective advantage for tumor cell survival in metastatic breast cancer PNAS, March 25, 2008; 105(12): 4850 - 4855. [Abstract] [Full Text] [PDF]

				Z. Hu, S. Shanker, J. A. MacLean II, S. L. Ackerman, and M. F. Wilkinson The RHOX5 Homeodomain Protein Mediates Transcriptional Repression of the Netrin-1 Receptor Gene Unc5c J. Biol. Chem., February 15, 2008; 283(7): 3866 - 3876. [Abstract] [Full Text] [PDF]

				M. Hammel, G. Sfyroera, S. Pyrpassopoulos, D. Ricklin, K. X. Ramyar, M. Pop, Z. Jin, J. D. Lambris, and B. V. Geisbrecht Characterization of Ehp, a Secreted Complement Inhibitory Protein from Staphylococcus aureus J. Biol. Chem., October 12, 2007; 282(41): 30051 - 30061. [Abstract] [Full Text] [PDF]

				S. Bouyain and D. J. Leahy Structure-based mutagenesis of the substrate-recognition domain of Nrdp1/FLRF identifies the binding site for the receptor tyrosine kinase ErbB3 Protein Sci., April 1, 2007; 16(4): 654 - 661. [Abstract] [Full Text] [PDF]

				I. Ben-Shlomo and A. J. W. Hsueh Three's Company: Two or More Unrelated Receptors Pair with the Same Ligand Mol. Endocrinol., May 1, 2005; 19(5): 1097 - 1109. [Abstract] [Full Text] [PDF]

				B. V. Geisbrecht, B. Y. Hamaoka, B. Perman, A. Zemla, and D. J. Leahy The Crystal Structures of EAP Domains from Staphylococcus aureus Reveal an Unexpected Homology to Bacterial Superantigens J. Biol. Chem., April 29, 2005; 280(17): 17243 - 17250. [Abstract] [Full Text] [PDF]

				R. P. Kruger, J. Lee, W. Li, and K.-L. Guan Mapping Netrin Receptor Binding Reveals Domains of Unc5 Regulating Its Tyrosine Phosphorylation J. Neurosci., December 1, 2004; 24(48): 10826 - 10834. [Abstract] [Full Text] [PDF]

				B. Y. Hamaoka, C. E. Dann III, B. V. Geisbrecht, and D. J. Leahy Crystal structure of Caenorhabditis elegans HER-1 and characterization of the interaction between HER-1 and TRA-2A PNAS, August 10, 2004; 101(32): 11673 - 11678. [Abstract] [Full Text] [PDF]