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

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Authors: Plant, L. D.; Marks, J. D.; Goldstein, S. A.
Article Title: SUMOylation of NaV1.2 channels mediates the early response to acute hypoxia in central neurons
Abstract: 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.
Journal Title: eLife
Volume: 5
ISSN: 2050-084X; 2050-084X
Publisher: Unknown  
Journal Place: England
Date Published: 2016
Start Page: 10.7554/eLife.20054
Language: eng
DOI/URL:

10.7554/eLife.20054
Notes: LR: 20170224; GR: R01 GM111716/GM/NIGMS NIH HHS/United States; GR: R01 NS056313/NS/NINDS NIH HHS/United States; GR: R01 NS058505/NS/NINDS NIH HHS/United States; JID: 101579614; OTO: NOTNLM; 2016/07/26 [received]; 2016/12/27 [accepted]; epublish