JCB logo
Keystone Symposia
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 14 July 2003. doi:10.1083/jcb.200301080
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dubreuil, C. I.
Right arrow Articles by McKerracher, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dubreuil, C. I.
Right arrow Articles by McKerracher, L.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0021-9525/2003/7/233 $5.00
The Journal of Cell Biology, Volume 162, Number 2, 233-243

Article

 Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system

Catherine I. Dubreuil, Matthew J. Winton and Lisa McKerracher

Département de pathologie et biologie cellulaire, Université de Montréal, Montréal, Québec H3T 1J4, Canada

Address correspondence to Lisa McKerracher, Université de Montréal, 2900 Edouard-Montpetit, Faculté de médecine, Département de pathologie et biologie cellulaire, Montréal, QC H3T 1J4, Canada. Tel.: (514) 343-6111, ex. 1472. Fax: (514) 282-9990. E-mail: mckerral{at}patho.umontreal.ca

Growth inhibitory proteins in the central nervous system (CNS) block axon growth and regeneration by signaling to Rho, an intracellular GTPase. It is not known how CNS trauma affects the expression and activation of RhoA. Here we detect GTP-bound RhoA in spinal cord homogenates and report that spinal cord injury (SCI) in both rats and mice activates RhoA over 10-fold in the absence of changes in RhoA expression. In situ Rho-GTP detection revealed that both neurons and glial cells showed Rho activation at SCI lesion sites. Application of a Rho antagonist (C3–05) reversed Rho activation and reduced the number of TUNEL-labeled cells by ~50% in both injured mouse and rat, showing a role for activated Rho in cell death after CNS injury. Next, we examined the role of the p75 neurotrophin receptor (p75NTR) in Rho signaling. After SCI, an up-regulation of p75NTR was detected by Western blot and observed in both neurons and glia. Treatment with C3–05 blocked the increase in p75NTR expression. Experiments with p75NTR-null mutant mice showed that immediate Rho activation after SCI is p75NTR dependent. Our results indicate that blocking overactivation of Rho after SCI protects cells from p75NTR-dependent apoptosis.

Key Words: spinal cord injury; RhoA; apoptosis; MAG; p75NTR

* Abbreviations used in this paper: CNS, central nervous system; MAG, myelin-associated glycoprotein; NgR, Nogo-66 receptor; p75NTR, p75 neurotrophin receptor; RBD, Rho-binding domain; SCI, spinal cord injury.


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


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents