Websomewhere in the signaling axis between CRMP2 and NaV1.7. The function of CRMP2 is controlled by its post-translational modification state [28,52–55]. We found that CRMP2-dependent regulation of NaV1.7 function is controlled by the addition of a small ubi-quitin-like modifier (SUMO) to CRMP2 at Lys374 by WebAs a case study, we present antinociceptive evidence of allosteric regulation of Na V 1.7 by the cytosolic collapsin response mediator protein 2 (CRMP2). Throughout discussions of these possible new targets, we offer thoughts on the therapeutic implications of modulating Na V 1.7 function in chronic pain.
Selective targeting of NaV1.7 via inhibition of the CRMP2 …
WebJan 21, 2024 · Our previous study established that non-SUMOylated CRMP2 recruits Numb, Nedd4-2 and Eps15 to regulate internalization of Na V 1.7 channels [ 25 ]. In basal … WebCo-opting this principle to CRMP2, we demonstrate that, of 3 sites predicted to be SUMOylated in CRMP2, only the lysine 374 site is a SUMOylation client. A reduction in NaV1.7 currents was the corollary of the loss of CRMP2 SUMOylation at this site. A 1.78-A -resolution crystal structure of mouse CRMP2 was solved using X-ray crystallography ... lahaina yacht club menu
Studies on CRMP2 SUMOylation–deficient transgenic mice... : PAIN
WebHypothesis: Here we test the hypothesis that a rationally designed NaV1.7-derived peptide can disrupt collapsin response mediator protein 2 (CRMP2)-NaV1.7 coupling. Methods: Using a peptide microarray, we report the discovery of a 15 amino acid regulatory sequence unique to NaV1.7 that is essential for its function. WebNov 25, 2024 · The researchers had previously shown that, when SUMOylated at lysine residue 374, CRMP2 promotes Nav1.7 expression on the plasma membrane, whereas restricting CRMP2-Lys374 SUMOylation... WebMar 1, 2024 · In Aim 1, we will test the general role of CRMP2 SUMOylation on Nav1.7 currents and neuronal excitability using a recently created new transgenic K374A Crmp2 knock-in mouse model where the SUMOylation site (K374) of CRMP2 has been replaced with an alanine mutation; this mouse was made by Dr. Thomas Doetschman, a co … je-je-jesus ist größer text