Regulation of CREB signaling through L-type Ca<sup>2+</sup>channels by Nipsnap-2

Brittain, Joel M.; Wang, Yuying; Wilson, Sarah M.; Khanna, Rajesh

doi:10.4161/chan.19415

Cited by 22 publications

(22 citation statements)

References 37 publications

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“…Lysates from these cells were immunoprecipitated (IP w/) with an anti-FLAG antibody. CaV1.2 was detected in CAD lysates expressing CRMP2 (top right blot) but not Nipsnap1 or -2, as reported previously (22). CAD cells express endogenous CaV1.2 (input lanes, top left blot).…”

Section: Ct-dis But Not L1 Peptide Affects K ϩ -Evoked Transmittermentioning

confidence: 50%

“…Transfection of CAD Cells-CAD cells were transfected using polyethyleneimine (PEI) as previously described (22). Briefly, cells were transfected at ϳ60% confluence using an experimentally optimized ratio of DNA/PEI.…”

Section: Methodsmentioning

confidence: 99%

“…The decrease in KCl-stimulated iCGRP A, CAD cells were transfected with cDNAs encoding Nipsnap-1-, Nipsnap-2-, or CRMP2-3xFLAG. We recently reported a novel role of Nipsnap2 in transcriptional regulation via L-type Ca 2ϩ channels (22). Lysates from these cells were immunoprecipitated (IP w/) with an anti-FLAG antibody.…”

Section: Ct-dis But Not L1 Peptide Affects K ϩ -Evoked Transmittermentioning

confidence: 99%

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Inhibition of Transmitter Release and Attenuation of Anti-retroviral-associated and Tibial Nerve Injury-related Painful Peripheral Neuropathy by Novel Synthetic Ca2+ Channel Peptides

Wilson

Schmutzler

Brittain

et al. 2012

Journal of Biological Chemistry

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Background: N-type Ca 2ϩ channels (CaV2.2) are clinically validated targets for chronic pain. Results: Two peptides from CaV2.2 and CaV1.2 perturb binding to a regulatory protein, CRMP2, inhibit calcium influx, and attenuate mechanical hyperalgesia in a rodent model of drug-induced chronic pain. Conclusion: Ca 2ϩ channel peptides block drug-and nerve injury-induced chronic pain. Significance: Ca 2ϩ channel peptide therapeutics can be useful in mitigating chronic pain.

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Section: Ct-dis But Not L1 Peptide Affects K ϩ -Evoked Transmittermentioning

confidence: 50%

Section: Methodsmentioning

confidence: 99%

Section: Ct-dis But Not L1 Peptide Affects K ϩ -Evoked Transmittermentioning

confidence: 99%

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Inhibition of Transmitter Release and Attenuation of Anti-retroviral-associated and Tibial Nerve Injury-related Painful Peripheral Neuropathy by Novel Synthetic Ca2+ Channel Peptides

Wilson

Schmutzler

Brittain

et al. 2012

Journal of Biological Chemistry

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“…24,53 For patch clamp experiments, CAD cells were transfected with 1 mg/ml of polyethyleneimine (PEI, Sigma) and 2 mg of various CRMP2 constructs. Under these conditions efficiencies of »50% were observed.…”

Section: Culturing and Transfection Of Catecholamine A Differentiatedmentioning

confidence: 99%

A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function

et al. 2017

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The neuronal collapsin response mediator protein 2 (CRMP2) undergoes several posttranslational modifications that codify its functions. Most recently, CRMP2 SUMOylation (addition of small ubiquitin like modifier (SUMO)) was identified as a key regulatory step within a modification program that codes for CRMP2 interaction with, and trafficking of, voltage-gated sodium channel NaV1.7. In this paper, we illustrate the utility of combining sequence alignment within protein families with structural analysis to identify, from several putative SUMOylation sites, those that are most likely to be biologically relevant. Co-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, revealing lysine 374 as buried within the CRMP2 tetramer interface but exposed in the monomer. Since CRMP2 SUMOylation is dependent on phosphorylation, we postulate that this state forces CRMP2 toward a monomer, exposing the SUMO site and consequently, resulting in constitutive regulation of NaV1.7.

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“…The neuronally derived CAD cells were grown at 37°C and in 5% CO 2 as previously described [30,31]. CAD cells were transfected as described above.…”

Section: Culturing Catecholamine a Differentiated (Cad) Cellsmentioning

confidence: 99%

Cdk5‐mediated phosphorylation of CRMP‐2 enhances its interaction with CaV2.2

et al. 2012

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Edited by Maurice Montal Keywords:CaV2.2 CRMP-2 Interaction Cdk5 RhoK Phosphorylation a b s t r a c tThe axon/dendrite specification collapsin response mediator protein-2 (CRMP-2) bidirectionally regulates N-type voltage-gated Ca 2+ channels (CaV2.2). But how cyclin dependent kinase 5 (Cdk5)-mediated phosphorylation of CRMP-2 affects its interaction/regulation with CaV2.2 is unknown. CRMP-2-mediated enhancement of currents via CaV2.2 was not observed with a Cdk5 phospho-null CRMP-2-S522A mutant or in cells expressing an inactive Cdk5. Concomitant knockdown of endogenous CRMP2 and overexpression of CRMP2-S522A mutant refractory to knockdown phenocopied the reduction in Ca 2+ influx while the Rho kinase CRMP2-T555A mutant was ineffective. Cdk5-phosphorylated CRMP-2 had increased association with CaV2.2. These results identify an important role for Cdk5 in CRMP2-mediated CaV2.2 regulation. Structured summary of protein interactions:Gsk3b phosphorylates Crmp2by phosphatase assay (View interaction) Crmp2 physically interacts with Cav2.2 by anti tag coimmunoprecipitation (View interaction)

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Regulation of CREB signaling through L-type Ca²⁺channels by Nipsnap-2

Cited by 22 publications

References 37 publications

Inhibition of Transmitter Release and Attenuation of Anti-retroviral-associated and Tibial Nerve Injury-related Painful Peripheral Neuropathy by Novel Synthetic Ca2+ Channel Peptides

Inhibition of Transmitter Release and Attenuation of Anti-retroviral-associated and Tibial Nerve Injury-related Painful Peripheral Neuropathy by Novel Synthetic Ca2+ Channel Peptides

A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function

Cdk5‐mediated phosphorylation of CRMP‐2 enhances its interaction with CaV2.2

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Regulation of CREB signaling through L-type Ca2+channels by Nipsnap-2

Cited by 22 publications

References 37 publications

Inhibition of Transmitter Release and Attenuation of Anti-retroviral-associated and Tibial Nerve Injury-related Painful Peripheral Neuropathy by Novel Synthetic Ca2+ Channel Peptides

Inhibition of Transmitter Release and Attenuation of Anti-retroviral-associated and Tibial Nerve Injury-related Painful Peripheral Neuropathy by Novel Synthetic Ca2+ Channel Peptides

A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function

Cdk5‐mediated phosphorylation of CRMP‐2 enhances its interaction with CaV2.2

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Regulation of CREB signaling through L-type Ca²⁺channels by Nipsnap-2