RGD Reference Report - SUMOylation of NaV1.2 channels mediates the early response to acute hypoxia in central neurons. - Rat Genome Database

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SUMOylation of NaV1.2 channels mediates the early response to acute hypoxia in central neurons.

Authors: Plant, Leigh D  Marks, Jeremy D  Goldstein, Steve An 
Citation: Plant LD, etal., Elife. 2016 Dec 28;5. doi: 10.7554/eLife.20054.
RGD ID: 14390052
Pubmed: (View Article at PubMed) PMID:28029095
DOI: Full-text: DOI:10.7554/eLife.20054

The mechanism for the earliest response of central neurons to hypoxia-an increase in voltage-gated sodium current (INa)-has been unknown. Here, we show that hypoxia activates the Small Ubiquitin-like Modifier (SUMO) pathway in rat cerebellar granule neurons (CGN) and that SUMOylation of NaV1.2 channels increases INa. The time-course for SUMOylation of single NaV1.2 channels at the cell surface and changes in INa coincide, and both are prevented by mutation of NaV1.2-Lys38 or application of a deSUMOylating enzyme. Within 40 s, hypoxia-induced linkage of SUMO1 to the channels is complete, shifting the voltage-dependence of channel activation so that depolarizing steps evoke larger sodium currents. Given the recognized role of INa in hypoxic brain damage, the SUMO pathway and NaV1.2 are identified as potential targets for neuroprotective interventions.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Scn2a  (sodium voltage-gated channel alpha subunit 2)


Additional Information