Next Article in Journal
A Comparative Study on the Biosorption of Cd2+ onto Paecilomyces lilacinus XLA and Mucoromycote sp. XLC
Next Article in Special Issue
ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells
Previous Article in Journal
Annona muricata (Annonaceae): A Review of Its Traditional Uses, Isolated Acetogenins and Biological Activities
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2015, 16(7), 15659-15669; doi:10.3390/ijms160715659

Impaired Focal Adhesion Kinase-Grb2 Interaction during Elevated Activity in Hippocampal Neurons

1
Laboratory of Molecular Biology, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
2
Department of Biology and Neuroscience and Cognitive Sciences Program, University of Maryland, College Park, MD 20742, USA
Academic Editor: Kurt A. Jellinger
Received: 5 May 2015 / Revised: 25 June 2015 / Accepted: 7 July 2015 / Published: 10 July 2015
(This article belongs to the Special Issue Mechanisms of Neurodegeneration)
View Full-Text   |   Download PDF [2610 KB, uploaded 10 July 2015]   |  

Abstract

Excitatory/inhibitory imbalances are implicated in many neurological disorders. Previously, we showed that chronically elevated network activity induces vulnerability in neurons due to loss of signal transducer and activator of transcription 3 (STAT3) signaling in response to the impairment of the serine/threonine kinase, extracellular-signal-regulated kinases 1/2 (Erk1/2) activation. However, how phosphorylation of Erk1/2 decreases during elevated neuronal activity was unknown. Here I show the pErk1/2 decrease induced by 4-aminopyridine (4-AP), an A-type potassium channel inhibitor can be blocked by a broad-spectrum matrix-metalloproteinase (MMP) inhibitor, FN-439. Surface expression levels of integrin β1 dramatically decrease when neurons are challenged by chronically elevated activity, which is reversed by FN-439. Treatment with 4-AP induces degradation of focal adhesion kinase (FAK), the mediator of integrin signaling. As a result, interactions between FAK and growth factor receptor-bound protein 2 (Grb2), the adaptor protein that mediates Erk1/2 activation by integrin, are severely impaired. Together, these data suggest the loss of integrin signaling during elevated activity causes vulnerability in neurons. View Full-Text
Keywords: focal adhesion kinase (FAK); Grb2; Erk1/2; signal transducer and activator of transcription 3 (STAT3); integrin β1; matrix-metalloproteinase (MMP); excitatory/inhibitory (E/I) balance; survival signaling focal adhesion kinase (FAK); Grb2; Erk1/2; signal transducer and activator of transcription 3 (STAT3); integrin β1; matrix-metalloproteinase (MMP); excitatory/inhibitory (E/I) balance; survival signaling
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Murase, S. Impaired Focal Adhesion Kinase-Grb2 Interaction during Elevated Activity in Hippocampal Neurons. Int. J. Mol. Sci. 2015, 16, 15659-15669.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top