QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 1, 2004, 24(48):10826-10834; doi:10.1523/JNEUROSCI.3715-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter 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 Web of Science 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 Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Kruger, R. P. Articles by Guan, K.-L. Search for Related Content PubMed PubMed Citation Articles by Kruger, R. P. Articles by Guan, K.-L.

 Previous Article  |  Next Article 

Cellular/Molecular
Mapping Netrin Receptor Binding Reveals Domains of Unc5 Regulating Its Tyrosine Phosphorylation

Robert P. Kruger,^1,2 Jeeyong Lee,^1,3 Weiquan Li,¹ and Kun-Liang Guan^1,3,4

¹Life Sciences Institute, ²Neuroscience Program, ³Department of Biological Chemistry, and ⁴Institute of Gerontology, University of Michigan, Ann Arbor, Michigan 48109

Netrin and its receptors Unc5 and deleted in colorectal carcinoma (DCC) regulate axon guidance and cell migration. We defined domains involved in the interactions between netrin-1, DCC, and Unc5c. We show that Unc5 requires both Ig domains to interact with netrin. DCC binds through the fourth fibronectin type III domain, whereas netrin binds through multiple domains to both receptors. We examined the functional consequences of removing the netrin binding and nonbinding domains from Unc5 in vitro and in vivo. In human embryonic kidney 293 cells, removal of the netrin binding second Ig domain causes an increase in basal tyrosine phosphorylation, whereas removal of the netrin nonbinding thrombospondin domains decreases tyrosine phosphorylation. Moreover, experiments in Caenorhabditis elegans indicate that both netrin binding and nonbinding domains are necessary for phenotypic rescue of an unc-5 loss of function mutation.

Key words: DCC; Unc5; netrin; axon guidance; receptor phosphorylation; cell migration

---

Received May 12, 2004; revised October 15, 2004; accepted October 18, 2004.

This article has been cited by other articles:

				A. Paradisi, C. Maisse, M.-M. Coissieux, N. Gadot, F. Lepinasse, C. Delloye-Bourgeois, J.-G. Delcros, M. Svrcek, C. Neufert, J.-F. Flejou, et al. Netrin-1 up-regulation in inflammatory bowel diseases is required for colorectal cancer progression PNAS, October 6, 2009; 106(40): 17146 - 17151. [Abstract] [Full Text] [PDF]

				R. Kuns-Hashimoto, D. Kuninger, M. Nili, and P. Rotwein Selective binding of RGMc/hemojuvelin, a key protein in systemic iron metabolism, to BMP-2 and neogenin Am J Physiol Cell Physiol, April 1, 2008; 294(4): C994 - C1003. [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]

				K.-i. Ogura and Y. Goshima The autophagy-related kinase UNC-51 and its binding partner UNC-14 regulate the subcellular localization of the Netrin receptor UNC-5 in Caenorhabditis elegans Development, September 1, 2006; 133(17): 3441 - 3450. [Abstract] [Full Text] [PDF]

				J. Lee, W. Li, and K.-L. Guan SRC-1 Mediates UNC-5 Signaling in Caenorhabditis elegans Mol. Cell. Biol., August 1, 2005; 25(15): 6485 - 6495. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help