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Regulation of Neuronal Ca(v)3.1 Channels by Cyclin-Dependent Kinase 5 (Cdk5)
Low voltage-activated (LVA) T-type Ca(2+) channels activate in response to subthreshold membrane depolarizations and therefore represent an important source of Ca(2+) influx near the resting membrane potential. In neurons, these proteins significantly contribute to control relevant physiological pro...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356599/ https://www.ncbi.nlm.nih.gov/pubmed/25760945 http://dx.doi.org/10.1371/journal.pone.0119134 |
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author | Calderón-Rivera, Aida Sandoval, Alejandro González-Ramírez, Ricardo González-Billault, Christian Felix, Ricardo |
author_facet | Calderón-Rivera, Aida Sandoval, Alejandro González-Ramírez, Ricardo González-Billault, Christian Felix, Ricardo |
author_sort | Calderón-Rivera, Aida |
collection | PubMed |
description | Low voltage-activated (LVA) T-type Ca(2+) channels activate in response to subthreshold membrane depolarizations and therefore represent an important source of Ca(2+) influx near the resting membrane potential. In neurons, these proteins significantly contribute to control relevant physiological processes including neuronal excitability, pacemaking and post-inhibitory rebound burst firing. Three subtypes of T-type channels (Ca(v)3.1 to Ca(v)3.3) have been identified, and using functional expression of recombinant channels diverse studies have validated the notion that T-type Ca(2+) channels can be modulated by various endogenous ligands as well as by second messenger pathways. In this context, the present study reveals a previously unrecognized role for cyclin-dependent kinase 5 (Cdk5) in the regulation of native T-type channels in N1E-115 neuroblastoma cells, as well as recombinant Ca(v)3.1channels heterologously expressed in HEK-293 cells. Cdk5 and its co-activators play critical roles in the regulation of neuronal differentiation, cortical lamination, neuronal cell migration and axon outgrowth. Our results show that overexpression of Cdk5 causes a significant increase in whole cell patch clamp currents through T-type channels in N1E-115 cells, while siRNA knockdown of Cdk5 greatly reduced these currents. Consistent with this, overexpression of Cdk5 in HEK-293 cells stably expressing Ca(v)3.1channels upregulates macroscopic currents. Furthermore, using site-directed mutagenesis we identified a major phosphorylation site at serine 2234 within the C-terminal region of the Ca(v)3.1subunit. These results highlight a novel role for Cdk5 in the regulation of T-type Ca(2+) channels. |
format | Online Article Text |
id | pubmed-4356599 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43565992015-03-17 Regulation of Neuronal Ca(v)3.1 Channels by Cyclin-Dependent Kinase 5 (Cdk5) Calderón-Rivera, Aida Sandoval, Alejandro González-Ramírez, Ricardo González-Billault, Christian Felix, Ricardo PLoS One Research Article Low voltage-activated (LVA) T-type Ca(2+) channels activate in response to subthreshold membrane depolarizations and therefore represent an important source of Ca(2+) influx near the resting membrane potential. In neurons, these proteins significantly contribute to control relevant physiological processes including neuronal excitability, pacemaking and post-inhibitory rebound burst firing. Three subtypes of T-type channels (Ca(v)3.1 to Ca(v)3.3) have been identified, and using functional expression of recombinant channels diverse studies have validated the notion that T-type Ca(2+) channels can be modulated by various endogenous ligands as well as by second messenger pathways. In this context, the present study reveals a previously unrecognized role for cyclin-dependent kinase 5 (Cdk5) in the regulation of native T-type channels in N1E-115 neuroblastoma cells, as well as recombinant Ca(v)3.1channels heterologously expressed in HEK-293 cells. Cdk5 and its co-activators play critical roles in the regulation of neuronal differentiation, cortical lamination, neuronal cell migration and axon outgrowth. Our results show that overexpression of Cdk5 causes a significant increase in whole cell patch clamp currents through T-type channels in N1E-115 cells, while siRNA knockdown of Cdk5 greatly reduced these currents. Consistent with this, overexpression of Cdk5 in HEK-293 cells stably expressing Ca(v)3.1channels upregulates macroscopic currents. Furthermore, using site-directed mutagenesis we identified a major phosphorylation site at serine 2234 within the C-terminal region of the Ca(v)3.1subunit. These results highlight a novel role for Cdk5 in the regulation of T-type Ca(2+) channels. Public Library of Science 2015-03-11 /pmc/articles/PMC4356599/ /pubmed/25760945 http://dx.doi.org/10.1371/journal.pone.0119134 Text en © 2015 Calderón-Rivera et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Calderón-Rivera, Aida Sandoval, Alejandro González-Ramírez, Ricardo González-Billault, Christian Felix, Ricardo Regulation of Neuronal Ca(v)3.1 Channels by Cyclin-Dependent Kinase 5 (Cdk5) |
title | Regulation of Neuronal Ca(v)3.1 Channels by Cyclin-Dependent Kinase 5 (Cdk5) |
title_full | Regulation of Neuronal Ca(v)3.1 Channels by Cyclin-Dependent Kinase 5 (Cdk5) |
title_fullStr | Regulation of Neuronal Ca(v)3.1 Channels by Cyclin-Dependent Kinase 5 (Cdk5) |
title_full_unstemmed | Regulation of Neuronal Ca(v)3.1 Channels by Cyclin-Dependent Kinase 5 (Cdk5) |
title_short | Regulation of Neuronal Ca(v)3.1 Channels by Cyclin-Dependent Kinase 5 (Cdk5) |
title_sort | regulation of neuronal ca(v)3.1 channels by cyclin-dependent kinase 5 (cdk5) |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356599/ https://www.ncbi.nlm.nih.gov/pubmed/25760945 http://dx.doi.org/10.1371/journal.pone.0119134 |
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