Impaired Focal Adhesion Kinase-Grb2 Interaction during Elevated Activity in Hippocampal Neurons
| dc.contributor.author | Murase, Sachiko | |
| dc.date.accessioned | 2024-01-10T19:14:01Z | |
| dc.date.available | 2024-01-10T19:14:01Z | |
| dc.date.issued | 2015-07-10 | |
| dc.description.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. | |
| dc.description.uri | https://doi.org/10.3390/ijms160715659 | |
| dc.identifier | https://doi.org/10.13016/dspace/ufd6-hyxe | |
| dc.identifier.citation | Murase, S. Impaired Focal Adhesion Kinase-Grb2 Interaction during Elevated Activity in Hippocampal Neurons. Int. J. Mol. Sci. 2015, 16, 15659-15669. | |
| dc.identifier.uri | http://hdl.handle.net/1903/31569 | |
| dc.language.iso | en_US | |
| dc.publisher | MDPI | |
| dc.relation.isAvailableAt | College of Computer, Mathematical & Physical Sciences | en_us |
| dc.relation.isAvailableAt | Digital Repository at the University of Maryland | en_us |
| dc.relation.isAvailableAt | Biology | en_us |
| dc.relation.isAvailableAt | University of Maryland (College Park, MD) | en_us |
| dc.subject | focal adhesion kinase (FAK) | |
| dc.subject | Grb2 | |
| dc.subject | Erk1/2 | |
| dc.subject | signal transducer and activator of transcription 3 (STAT3) | |
| dc.subject | matrix-metalloproteinase (MMP) | |
| dc.subject | excitatory/inhibitory (E/I) balance | |
| dc.subject | survival signaling | |
| dc.title | Impaired Focal Adhesion Kinase-Grb2 Interaction during Elevated Activity in Hippocampal Neurons | |
| dc.type | Article | |
| local.equitableAccessSubmission | No |