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Publication : Activity dependent dissociation of the Homer1 interactome.

First Author  Stillman M Year  2022
Journal  Sci Rep Volume  12
Issue  1 Pages  3207
PubMed ID  35217690 Mgi Jnum  J:322555
Mgi Id  MGI:6887138 Doi  10.1038/s41598-022-07179-3
Citation  Stillman M, et al. (2022) Activity dependent dissociation of the Homer1 interactome. Sci Rep 12(1):3207
abstractText  Neurons encode information by rapidly modifying synaptic protein complexes, which changes the strength of specific synaptic connections. Homer1 is abundantly expressed at glutamatergic synapses, and is known to alter its binding to metabotropic glutamate receptor 5 (mGlu5) in response to synaptic activity. However, Homer participates in many additional known interactions whose activity-dependence is unclear. Here, we used co-immunoprecipitation and label-free quantitative mass spectrometry to characterize activity-dependent interactions in the cerebral cortex of wildtype and Homer1 knockout mice. We identified a small, high-confidence protein network consisting of mGlu5, Shank2 and 3, and Homer1-3, of which only mGlu5 and Shank3 were significantly reduced following neuronal depolarization. We identified several other proteins that reduced their co-association in an activity-dependent manner, likely mediated by Shank proteins. We conclude that Homer1 dissociates from mGlu5 and Shank3 following depolarization, but our data suggest that direct Homer1 interactions in the cortex may be more limited than expected.
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