MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Other Versions of this Article:
MCB.00948-07v1
27/24/8698    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Garg, P.
Right arrow Articles by Holzman, L. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Garg, P.
Right arrow Articles by Holzman, L. B.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2007, p. 8698-8712, Vol. 27, No. 24
0270-7306/07/$08.00+0     doi:10.1128/MCB.00948-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Neph1 Cooperates with Nephrin To Transduce a Signal That Induces Actin Polymerization{triangledown}

Puneet Garg,1,{dagger} Rakesh Verma,1,{dagger} Deepak Nihalani,3 Duncan B. Johnstone,1 and Lawrence B. Holzman1,2*

Division of Nephrology, University of Michigan Medical School, Ann Arbor, Michigan 48109,1 Department of Veterans Affairs, Ann Arbor, Michigan 48105,2 Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana 462023

Received 29 May 2007/ Returned for modification 13 July 2007/ Accepted 28 September 2007

While the mechanisms that regulate actin dynamics in cellular motility are intensively studied, relatively little is known about signaling events that transmit outside-in signals and direct assembly and regulation of actin polymerization complexes at the cell membrane. The kidney podocyte provides a unique model for investigating these mechanisms since deletion of Nephrin or Neph1, two interacting components of the specialized podocyte intercellular junction, results in abnormal podocyte morphogenesis and junction formation. We provide evidence that extends the existing model by which the Nephrin-Neph1 complex transduces phosphorylation-mediated signals that assemble an actin polymerization complex at the podocyte intercellular junction. Upon engagement, Neph1 is phosphorylated on specific tyrosine residues by Fyn, which results in the recruitment of Grb2, an event that is necessary for Neph1-induced actin polymerization at the plasma membrane. Importantly, Neph1 and Nephrin directly interact and, by juxtaposing Grb2 and Nck1/2 at the membrane following complex activation, cooperate to augment the efficiency of actin polymerization. These data provide evidence for a mechanism reminiscent of that employed by vaccinia virus and other pathogens, by which a signaling complex transduces an outside-in signal that results in actin filament polymerization at the plasma membrane.

* Corresponding author. Mailing address: University of Michigan Medical School, Division of Nephrology, 1560 Medical Science Research Building II, Ann Arbor, MI 48109-5676. Phone: (734) 764-3157. Fax: (734) 763-0982. E-mail: lholzman{at}umich.edu

{triangledown} Published ahead of print on 8 October 2007.

{dagger} These authors contributed equally to this work.

Molecular and Cellular Biology, December 2007, p. 8698-8712, Vol. 27, No. 24
0270-7306/07/$08.00+0     doi:10.1128/MCB.00948-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2007 by the American Society for Microbiology. All rights reserved.