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Papers of the Week

Papers: 23 Jan 2021 - 29 Jan 2021

Animal Studies

2021 Jan 21

Mol Brain



Non-SUMOylated CRMP2 decreases Na1.7 currents via the endocytic proteins Numb, Nedd4-2 and Eps15.


Gomez K, Ran D, Madura CL, Moutal A, Khanna R
Mol Brain. 2021 Jan 21; 14(1):20.
PMID: 33478555.


Voltage-gated sodium channels are key players in neuronal excitability and pain signaling. Functional expression of the voltage-gated sodium channel Na1.7 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 Na1.7. We recently reported that CRMP2 SUMO-null knock-in (CRMP2) female mice have reduced Na1.7 membrane localization and currents in their sensory neurons. Preventing CRMP2 SUMOylation was sufficient to reverse mechanical allodynia in CRMP2 female mice with neuropathic pain. Here we report that inhibiting clathrin assembly in nerve-injured male CRMP2 mice precipitated mechanical allodynia in mice otherwise resistant to developing persistent pain. Furthermore, Numb, Nedd4-2 and Eps15 expression was not modified in basal conditions in the dorsal root ganglia (DRG) of male and female CRMP2 mice. Finally, silencing these proteins in DRG neurons from female CRMP2 mice, restored the loss of sodium currents. Our study shows that the endocytic complex composed of Numb, Nedd4-2 and Eps15, is necessary for non-SUMOylated CRMP2-mediated internalization of sodium channels in vivo.