Non-SUMOylated CRMP2 decreases Na_V1.7 currents via the endocytic proteins Numb, Nedd4-2 and Eps15.

ABSTRACT: Voltage-gated sodium channels are key players in neuronal excitability and pain signaling. Functional expression of the voltage-gated sodium channel Na_V1.7 is under the control of SUMOylated collapsin response mediator protein 2 (CRMP2). When not SUMOylated, CRMP2 forms a complex with the endocytic proteins Numb, the epidermal growth factor receptor pathway substrate 15 (Eps15), and the E3 ubiquitin ligase Nedd4-2 to promote clathrin-mediated endocytosis of Na_V1.7. We recently reported that CRMP2 SUMO-null knock-in (CRMP2^K374A/K374A) female mice have reduced Na_V1.7 membrane localization and currents in their sensory neurons. Preventing CRMP2 SUMOylation was sufficient to reverse mechanical allodynia in CRMP2^K374A/K374A female mice with

SUBMITTER: Gomez K 

PROVIDER: S-EPMC7819318 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature