Pin1 Binding to Phosphorylated PSD-95 Regulates the Number of Functional Excitatory Synapses
Autor: | Paul R. Selvin, Jary Y. Delgado, Duncan L. Nall |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
post-synaptic density protein 95 excitatory synaptic transmission AMPA receptor lcsh:RC321-571 03 medical and health sciences Cellular and Molecular Neuroscience Pin1 0302 clinical medicine Excitatory synapse cis–trans isomerization Palmitoylation proline-directed phosphorylation mental disorders palmitoylation lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Molecular Biology Original Research Chemistry musculoskeletal neural and ocular physiology Cis trans isomerization Cell biology 030104 developmental biology nervous system Synaptic plasticity Excitatory postsynaptic potential PIN1 Phosphorylation psychological phenomena and processes 030217 neurology & neurosurgery Neuroscience |
Zdroj: | Frontiers in Molecular Neuroscience, Vol 13 (2020) Frontiers in Molecular Neuroscience |
ISSN: | 1662-5099 |
DOI: | 10.3389/fnmol.2020.00010 |
Popis: | The post-synaptic density protein 95 (PSD-95) plays a central role in excitatory synapse development and synaptic plasticity. Phosphorylation of the N-terminus of PSD-95 at threonine 19 (T19) and serine 25 (S25) decreases PSD-95 stability at synapses; however, a molecular mechanism linking PSD-95 phosphorylation to altered synaptic stability is lacking. Here, we show that phosphorylation of T19/S25 recruits the phosphorylation-dependent peptidyl-prolyl cis–trans isomerase (Pin1) and reduces the palmitoylation of Cysteine 3 and Cysteine 5 in PSD-95. This reduction in PSD-95 palmitoylation accounts for the observed loss in the number of dendritic PSD-95 clusters, the increased AMPAR mobility, and the decreased number of functional excitatory synapses. We find the effects of Pin1 overexpression were all rescued by manipulations aimed at increasing the levels of PSD-95 palmitoylation. Therefore, Pin1 is a key signaling molecule that regulates the stability of excitatory synapses and may participate in the destabilization of PSD-95 following the induction of synaptic plasticity. |
Databáze: | OpenAIRE |
Externí odkaz: |