Shank is a dose-dependent regulator of Ca(v)1 calcium current and CREB target expression

Shank is a post-synaptic scaffolding protein that has many binding partners. Shank mutations and copy number variations (CNVs) are linked to several psychiatric disorders, and to synaptic and behavioral defects in mice. It is not known which Shank binding partners are responsible for these defects....

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Autores principales: Pym, Edward, Sasidharan, Nikhil, Thompson-Peer, Katherine L, Simon, David J, Anselmo, Anthony, Sadreyev, Ruslan, Hall, Qi, Nurrish, Stephen, Kaplan, Joshua M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Neuroscience
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432211/
https://www.ncbi.nlm.nih.gov/pubmed/28477407
http://dx.doi.org/10.7554/eLife.18931
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author Pym, Edward
Sasidharan, Nikhil
Thompson-Peer, Katherine L
Simon, David J
Anselmo, Anthony
Sadreyev, Ruslan
Hall, Qi
Nurrish, Stephen
Kaplan, Joshua M
author_facet Pym, Edward
Sasidharan, Nikhil
Thompson-Peer, Katherine L
Simon, David J
Anselmo, Anthony
Sadreyev, Ruslan
Hall, Qi
Nurrish, Stephen
Kaplan, Joshua M
author_sort Pym, Edward
collection PubMed
description Shank is a post-synaptic scaffolding protein that has many binding partners. Shank mutations and copy number variations (CNVs) are linked to several psychiatric disorders, and to synaptic and behavioral defects in mice. It is not known which Shank binding partners are responsible for these defects. Here we show that the C. elegans SHN-1/Shank binds L-type calcium channels and that increased and decreased shn-1 gene dosage alter L-channel current and activity-induced expression of a CRH-1/CREB transcriptional target (gem-4 Copine), which parallels the effects of human Shank copy number variations (CNVs) on Autism spectrum disorders and schizophrenia. These results suggest that an important function of Shank proteins is to regulate L-channel current and activity induced gene expression. DOI: http://dx.doi.org/10.7554/eLife.18931.001
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spelling pubmed-54322112017-05-17 Shank is a dose-dependent regulator of Ca(v)1 calcium current and CREB target expression Pym, Edward Sasidharan, Nikhil Thompson-Peer, Katherine L Simon, David J Anselmo, Anthony Sadreyev, Ruslan Hall, Qi Nurrish, Stephen Kaplan, Joshua M eLife Neuroscience Shank is a post-synaptic scaffolding protein that has many binding partners. Shank mutations and copy number variations (CNVs) are linked to several psychiatric disorders, and to synaptic and behavioral defects in mice. It is not known which Shank binding partners are responsible for these defects. Here we show that the C. elegans SHN-1/Shank binds L-type calcium channels and that increased and decreased shn-1 gene dosage alter L-channel current and activity-induced expression of a CRH-1/CREB transcriptional target (gem-4 Copine), which parallels the effects of human Shank copy number variations (CNVs) on Autism spectrum disorders and schizophrenia. These results suggest that an important function of Shank proteins is to regulate L-channel current and activity induced gene expression. DOI: http://dx.doi.org/10.7554/eLife.18931.001 eLife Sciences Publications, Ltd 2017-05-06 /pmc/articles/PMC5432211/ /pubmed/28477407 http://dx.doi.org/10.7554/eLife.18931 Text en © 2017, Pym et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Pym, Edward
Sasidharan, Nikhil
Thompson-Peer, Katherine L
Simon, David J
Anselmo, Anthony
Sadreyev, Ruslan
Hall, Qi
Nurrish, Stephen
Kaplan, Joshua M
Shank is a dose-dependent regulator of Ca(v)1 calcium current and CREB target expression
title Shank is a dose-dependent regulator of Ca(v)1 calcium current and CREB target expression
title_full Shank is a dose-dependent regulator of Ca(v)1 calcium current and CREB target expression
title_fullStr Shank is a dose-dependent regulator of Ca(v)1 calcium current and CREB target expression
title_full_unstemmed Shank is a dose-dependent regulator of Ca(v)1 calcium current and CREB target expression
title_short Shank is a dose-dependent regulator of Ca(v)1 calcium current and CREB target expression
title_sort shank is a dose-dependent regulator of ca(v)1 calcium current and creb target expression
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432211/
https://www.ncbi.nlm.nih.gov/pubmed/28477407
http://dx.doi.org/10.7554/eLife.18931
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