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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 24, 2009, 29(25):8129-8142; doi:10.1523/JNEUROSCI.4681-08.2009

This Article Full Text Full Text (PDF) Supplemental Data 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 Related articles in J. Neurosci. 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 Google Scholar Articles by Shi, Y. Articles by Ethell, I. M. PubMed PubMed Citation Articles by Shi, Y. Articles by Ethell, I. M.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Focal Adhesion Kinase Acts Downstream of EphB Receptors to Maintain Mature Dendritic Spines by Regulating Cofilin Activity

Yang Shi,¹ Crystal G. Pontrello,¹ Kathryn A. DeFea,¹ Louis F. Reichardt,² and Iryna M. Ethell¹

¹Division of Biomedical Sciences and Neuroscience Program, University of California, Riverside, Riverside, California 92521, and ²Department of Physiology, University of California, San Francisco, San Francisco, California 94158

Correspondence should be addressed to Dr. Iryna Ethell, Biomedical Sciences, University of California, Riverside, 900 University Avenue, Riverside, CA 92521-0121. Email: iryna.ethell{at}ucr.edu

Dendritic spines are the postsynaptic sites of most excitatory synapses in the brain and are highly enriched in polymerized F-actin, which drives the formation and maintenance of mature dendritic spines and synapses. We propose that suppressing the activity of the actin-severing protein cofilin plays an important role in the stabilization of mature dendritic spines, and is accomplished through an EphB receptor–focal adhesion kinase (FAK) pathway. Our studies revealed that Cre-mediated knock-out of loxP-flanked fak prompted the reversion of mature dendritic spines to an immature filopodial-like phenotype in primary hippocampal cultures. The effects of FAK depletion on dendritic spine number, length, and morphology were rescued by the overexpression of the constitutively active FAK^Y397E, but not FAK^Y397F, indicating the significance of FAK activation by phosphorylation on tyrosine 397. Our studies demonstrate that FAK acts downstream of EphB receptors in hippocampal neurons and EphB2–FAK signaling controls the stability of mature dendritic spines by promoting cofilin phosphorylation, thereby inhibiting cofilin activity. While constitutively active nonphosphorylatable cofilin^S3A induced an immature spine profile, phosphomimetic cofilin^S3D restored mature spine morphology in neurons with disrupted EphB activity or lacking FAK. Further, we found that EphB-mediated regulation of cofilin activity at least partially depends on the activation of Rho-associated kinase (ROCK) and LIMK-1. These findings indicate that EphB2-mediated dendritic spine stabilization relies, in part, on the ability of FAK to activate the RhoA–ROCK–LIMK-1 pathway, which functions to suppress cofilin activity and inhibit cofilin-mediated dendritic spine remodeling.

---

Received Sept. 30, 2008; revised May 20, 2009; accepted May 23, 2009.

Correspondence should be addressed to Dr. Iryna Ethell, Biomedical Sciences, University of California, Riverside, 900 University Avenue, Riverside, CA 92521-0121. Email: iryna.ethell{at}ucr.edu

Related articles in J. Neurosci.:

EphB Maintains Dendritic Spine Morphology through Focal Adhesion Kinase

Yu Chen and Wing-Yu Fu
J. Neurosci. 2009 29: 13091-13093. [Full Text]  

This article has been cited by other articles:

				Y. Chen and W.-Y. Fu EphB Maintains Dendritic Spine Morphology through Focal Adhesion Kinase J. Neurosci., October 21, 2009; 29(42): 13091 - 13093. [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help