SUMOylation alters CRMP2 regulation of calcium influx in sensory neurons

Weina Ju; Qi Li; Sarah M. Wilson; Joel M. Brittain; Louay Meroueh; Rajesh Khanna

doi:10.4161/chan.24224

SUMOylation alters CRMP2 regulation of calcium influx in sensory neurons

Weina Ju
, Qi Li
, Sarah M. Wilson
, Joel M. Brittain
, Louay Meroueh
, Rajesh Khanna

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

The axon/dendrite specification collapsin response mediator protein 2 (CRMP2) bidirectionally modulates N-type voltagegated Ca²⁺ 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; CRMP2_AAA) 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 de SUMOylation by SUMO proteases SENP1 and SENP2 normalized calcium influx to those in the CRMP2 _AAA mutant. Thus, our results identify a novel role for SUMO modification in CRMP2/CaV2.2 signaling pathway.

Original language	English (US)
Pages (from-to)	153-159
Number of pages	7
Journal	Channels
Volume	7
Issue number	3
DOIs	https://doi.org/10.4161/chan.24224
State	Published - 2013
Externally published	Yes

Keywords

CRMP2
CaV2.2
Calcium influx
SUMO
Sensory neurons
Ubc9

ASJC Scopus subject areas

Biophysics
Biochemistry

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10.4161/chan.24224

Cite this

@article{00958e88d34949f58b827d5b258ec8d4,

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 voltagegated Ca2+ 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 de SUMOylation by SUMO proteases SENP1 and SENP2 normalized calcium influx to those in the CRMP2 AAA mutant. Thus, our results identify a novel role for SUMO modification in CRMP2/CaV2.2 signaling pathway.",

keywords = "CRMP2, CaV2.2, Calcium influx, SUMO, Sensory neurons, Ubc9",

author = "Weina Ju and Qi Li and Wilson, \{Sarah M.\} and Brittain, \{Joel M.\} and Louay Meroueh and Rajesh Khanna",

note = "Funding Information: We thank Erik Dustrude, Dr May Khanna for helpful discussions, and Dr Fletcher A. White for generous use of his calcium imaging microscope. This work was supported, in part, by grants from the Indiana Clinical and Translational Sciences Funding Information: Institute funded, in part by a Project Development Team Grant Number (RR025761) from the National Institutes of Health (NIH), National Center for Research Resources, Clinical and Funding Information: Translational Sciences Award, the Indiana State Department of Health—Spinal Cord and Brain Injury Fund (A70-9-079138 to R.K.), a National Scientist Development grant from the American Heart Association (SDG5280023 to R.K.), a Neurofibromatosis New Investigator Award from the Department of Defense Congressionally Directed Military Medical Research and Development Program (NF1000099 to R.K.), and a Ralph and Grace Showalter Trust Foundation award (to R.K.). S.M.W. was partially supported by a Stark Medical Neuroscience Fellowship.",

year = "2013",

doi = "10.4161/chan.24224",

language = "English (US)",

volume = "7",

pages = "153--159",

journal = "Channels",

issn = "1933-6950",

publisher = "Taylor and Francis Ltd.",

number = "3",

}

TY - JOUR

T1 - SUMOylation alters CRMP2 regulation of calcium influx in sensory neurons

AU - Ju, Weina

AU - Li, Qi

AU - Wilson, Sarah M.

AU - Brittain, Joel M.

AU - Meroueh, Louay

AU - Khanna, Rajesh

N1 - Funding Information: We thank Erik Dustrude, Dr May Khanna for helpful discussions, and Dr Fletcher A. White for generous use of his calcium imaging microscope. This work was supported, in part, by grants from the Indiana Clinical and Translational Sciences Funding Information: Institute funded, in part by a Project Development Team Grant Number (RR025761) from the National Institutes of Health (NIH), National Center for Research Resources, Clinical and Funding Information: Translational Sciences Award, the Indiana State Department of Health—Spinal Cord and Brain Injury Fund (A70-9-079138 to R.K.), a National Scientist Development grant from the American Heart Association (SDG5280023 to R.K.), a Neurofibromatosis New Investigator Award from the Department of Defense Congressionally Directed Military Medical Research and Development Program (NF1000099 to R.K.), and a Ralph and Grace Showalter Trust Foundation award (to R.K.). S.M.W. was partially supported by a Stark Medical Neuroscience Fellowship.

PY - 2013

Y1 - 2013

N2 - The axon/dendrite specification collapsin response mediator protein 2 (CRMP2) bidirectionally modulates N-type voltagegated Ca2+ 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 de SUMOylation by SUMO proteases SENP1 and SENP2 normalized calcium influx to those in the CRMP2 AAA mutant. Thus, our results identify a novel role for SUMO modification in CRMP2/CaV2.2 signaling pathway.

AB - The axon/dendrite specification collapsin response mediator protein 2 (CRMP2) bidirectionally modulates N-type voltagegated Ca2+ 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 de SUMOylation by SUMO proteases SENP1 and SENP2 normalized calcium influx to those in the CRMP2 AAA mutant. Thus, our results identify a novel role for SUMO modification in CRMP2/CaV2.2 signaling pathway.

KW - CRMP2

KW - CaV2.2

KW - Calcium influx

KW - SUMO

KW - Sensory neurons

KW - Ubc9

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SP - 153

EP - 159

JO - Channels

JF - Channels

IS - 3

ER -

SUMOylation alters CRMP2 regulation of calcium influx in sensory neurons

Abstract

Keywords

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