Figure 1. CRMP2 and ion channel signaling.

Cav2.2 and Nav1.7 channels exist in at least two pools – membrane-delimited and cytosolic. Cdk5-mediated phosphorylation of CRMP2 (at Ser⁵²²) and CRMP2-binding with syntaxin 1A facilitate the CRMP2–Cav2.2 interaction and increased Cav2.2 membrane insertion. In a parallel process, CRMP2 phosphorylation by Cdk5 supports CRMP2 SUMOylation (at Lys³⁷⁴) and subsequent increased Nav1.7 trafficking and surface expression.