Proteomics

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Temporal quantitative proteomics of mGluR-induced protein translation and phosphorylation in neurons


ABSTRACT: At neuronal synapses, activation of group I metabotropic glutamate receptors (mGluR1/5) triggers a form of long-term depression (mGluR-LTD) that relies on new protein synthesis and the internalization of AMPA-type glutamate receptors. Dysregulation of these processes has been implicated in the development of mental disorders such as autism spectrum disorders and therefore merit a better understanding on a molecular level. Here, to study mGluR-induced signaling pathways, we integrated quantitative phosphoproteomics with the analyses of newly synthesized proteins via bio-orthogonal amino acids (azidohomoalanine) in a pulsed labeling strategy in cultured hippocampal neurons stimulated with DHPG, a specific agonist for group I mGluRs. We identified several kinases with important roles in DHPG-induced mGluR activation, which we confirmed using small molecule kinase inhibitors. Furthermore, changes in the AMPA receptor endocytosis pathway in both protein synthesis and protein phosphorylation were identified, whereby Intersectin-1 was validated as a novel player in this pathway. This study revealed several new insights into the molecular pathways downstream of group I mGluR activation in hippocampal neurons, and provides a rich resource for further analyses.

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Tim Veth  

PROVIDER: PXD020777 | panorama | Tue Oct 27 00:00:00 GMT 2020

REPOSITORIES: PanoramaPublic

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Temporal Quantitative Proteomics of mGluR-induced Protein Translation and Phosphorylation in Neurons.

van Gelder Charlotte A G H CAGH   Penning Renske R   Veth Tim S TS   Catsburg Lisa A E LAE   Hoogenraad Casper C CC   MacGillavry Harold D HD   Altelaar Maarten M  

Molecular & cellular proteomics : MCP 20200910 12


At neuronal synapses, activation of group I metabotropic glutamate receptors (mGluR1/5) triggers a form of long-term depression (mGluR-LTD) that relies on new protein synthesis and the internalization of AMPA-type glutamate receptors. Dysregulation of these processes has been implicated in the development of mental disorders such as autism spectrum disorders and therefore merit a better understanding on a molecular level. Here, to study mGluR-induced signaling pathways, we integrated quantitativ  ...[more]

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