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Regulation and function of activity-dependent Homer in synaptic plasticity

Clifton, Nicholas, Trent, Simon, Thomas, Kerrie and Hall, Jeremy 2019. Regulation and function of activity-dependent Homer in synaptic plasticity. Molecular Neuropsychiatry 5 (3) , pp. 147-161. 10.1159/000500267

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Abstract

Alterations in synaptic signaling and plasticity occur during the refinement of neural circuits over the course of development and the adult processes of learning and memory. Synaptic plasticity requires the rearrangement of protein complexes in the postsynaptic density (PSD), trafficking of receptors and ion channels and the synthesis of new proteins. Activity-induced short Homer proteins, Homer1a and Ania-3, are recruited to active excitatory synapses, where they act as dominant negative regulators of constitutively expressed, longer Homer isoforms. The expression of Homer1a and Ania-3 initiates critical processes of PSD remodeling, the modulation of glutamate receptor-mediated functions, and the regulation of calcium signaling. Together, available data support the view that Homer1a and Ania-3 are responsible for the selective, transient destabilization of postsynaptic signaling complexes to facilitate plasticity of the excitatory synapse. The interruption of activity-dependent Homer proteins disrupts disease-relevant processes and leads to memory impairments, reflecting their likely contribution to neurological disorders.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Medicine
Publisher: Karger Publishers
ISSN: 2296-9209
Funders: Wellcome Trust, Medical Research Council
Date of First Compliant Deposit: 16 April 2019
Date of Acceptance: 9 April 2019
Last Modified: 29 Jun 2019 00:02
URI: http://orca.cf.ac.uk/id/eprint/121784

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