title: SUMOylation alters CRMP2 regulation of calcium influx in sensory neurons.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Weina
authors.initials: W
authors.lastname: Ju
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Wilson
authors.forename: Joel M
authors.initials: JM
authors.lastname: Brittain
authors.forename: Louay
authors.initials: L
authors.lastname: Meroueh
authors.forename: Rajesh
authors.initials: R
authors.lastname: Khanna
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation
chemical_list: D015220:Calcium Channels; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C095114:collapsin response mediator protein-2; D002118:Calcium
keywords: CRMP2; CaV2.2; SUMO; Ubc9; calcium influx; sensory neurons