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Regulation of Neuronal Cav3.1 Channels by Cyclin-Dependent Kinase 5 (Cdk5)
| Content Provider | Semantic Scholar |
|---|---|
| Author | Calderón-Rivera, Aida Sandoval, Alejandro González-Ramírez, Ricardo González-Billault, Christian Félix, Ricardo |
| Copyright Year | 2015 |
| Abstract | Low voltage-activated (LVA) T-type Ca2+ channels activate in response to subthreshold membrane depolarizations and therefore represent an important source of Ca2+ 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 (Cav3.1 to Cav3.3) have been identified, and using functional expression of recombinant channels diverse studies have validated the notion that T-type Ca2+ 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 Cav3.1channels 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 Cav3.1channels upregulates macroscopic currents. Furthermore, using site-directed mutagenesis we identified a major phosphorylation site at serine 2234 within the C-terminal region of the Cav3.1subunit. These results highlight a novel role for Cdk5 in the regulation of T-type Ca2+ channels. |
| File Format | PDF HTM / HTML |
| DOI | 10.1371/journal.pone.0119134 |
| PubMed reference number | 25760945 |
| Journal | Medline |
| Volume Number | 10 |
| Alternate Webpage(s) | http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0119134&type=printable |
| Alternate Webpage(s) | https://doi.org/10.1371/journal.pone.0119134 |
| Journal | PloS one |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
