JCB logo
MBL International Tel: 800.200.5459 CLICK HERE
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online
doi:10.1083/jcb.200610139
The Journal of Cell Biology, Vol. 178, No. 7, 1295-1307
The Rockefeller University Press, 0021-9525 $30.00
© Bourgin et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2727K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
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 Bourgin, C.
Right arrow Articles by Pasquale, E. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bourgin, C.
Right arrow Articles by Pasquale, E. B.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Article

The EphA4 receptor regulates dendritic spine remodeling by affecting ß1-integrin signaling pathways



Caroline Bourgin1, Keith K. Murai2, Melanie Richter1, and Elena B. Pasquale1,3

1 Burnham Institute for Medical Research, La Jolla, CA 92037
2 Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, McGill University Health Centre, Montreal General Hospital, Quebec H3G 1A4, Canada
3 Pathology Department, University of California, San Diego, La Jolla, CA 92093

Correspondence to Elena B. Pasquale: elenap{at}burnham.org

Remodeling of dendritic spines is believed to modulate the function of excitatory synapses. We previously reported that the EphA4 receptor tyrosine kinase regulates spine morphology in hippocampal pyramidal neurons, but the signaling pathways involved were not characterized (Murai, K.K., L.N. Nguyen, F. Irie, Y. Yamaguchi, and E.B. Pasquale. 2003. Nat. Neurosci. 6:153–160). In this study, we show that EphA4 activation by ephrin-A3 in hippocampal slices inhibits integrin downstream signaling pathways. EphA4 activation decreases tyrosine phosphorylation of the scaffolding protein Crk-associated substrate (Cas) and the tyrosine kinases focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) and also reduces the association of Cas with the Src family kinase Fyn and the adaptor Crk. Consistent with this, EphA4 inhibits ß1-integrin activity in neuronal cells. Supporting a functional role for ß1 integrin and Cas inactivation downstream of EphA4, the inhibition of integrin or Cas function induces spine morphological changes similar to those associated with EphA4 activation. Furthermore, preventing ß1-integrin inactivation blocks the effects of EphA4 on spines. Our results support a model in which EphA4 interferes with integrin signaling pathways that stabilize dendritic spines, thus modulating synaptic interactions with the extracellular environment.

Abbreviations used in this paper: ANOVA, analysis of variance; Cas, Crk- associated substrate; EGFP-F, farnesylated enhanced GFP; FAK, focal adhesion kinase; LTP, long-term potentiation; NMDA, N-methyl-D-aspartate; PSD, postsynaptic density; Pyk2, proline-rich tyrosine kinase 2.


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



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