The axon/dendrite specification collapsin response mediator protein 2 (CRMP2) 
bidirectionally modulates N-type voltage-gated Ca ( 2+) channels (CaV2.2). Here 
we demonstrate that small ubiquitin-like modifier (SUMO) protein modifies CRMP2 
via the SUMO E2-conjugating enzyme Ubc9 in vivo. Removal of a SUMO conjugation 
site KMD in CRMP2 (K374A/M375A/D376A; CRMP2AAA) resulted in loss of SUMOylated 
CRMP2 without compromising neurite branching, a canonical hallmark of CRMP2 
function. Increasing SUMOylation levels correlated inversely with calcium influx 
in sensory neurons. CRMP2 deSUMOylation by SUMO proteases SENP1 and SENP2 
normalized calcium influx to those in the CRMP2AAA mutant. Thus, our results 
identify a novel role for SUMO modification in CRMP2/CaV2.2 signaling pathway.