Dissecting the role of the CRMP2-neurofibromin complex on pain behaviors

Pain
Aubin MoutalRajesh Khanna

Abstract

Neurofibromatosis type 1 (NF1), a genetic disorder linked to inactivating mutations or a homozygous deletion of the Nf1 gene, is characterized by tumorigenesis, cognitive dysfunction, seizures, migraine, and pain. Omic studies on human NF1 tissues identified an increase in the expression of collapsin response mediator protein 2 (CRMP2), a cytosolic protein reported to regulate the trafficking and activity of presynaptic N-type voltage-gated calcium (Cav2.2) channels. Because neurofibromin, the protein product of the Nf1 gene, binds to and inhibits CRMP2, the neurofibromin-CRMP2 signaling cascade will likely affect Ca channel activity and regulate nociceptive neurotransmission and in vivo responses to noxious stimulation. Here, we investigated the function of neurofibromin-CRMP2 interaction on Cav2.2. Mapping of >275 peptides between neurofibromin and CRMP2 identified a 15-amino acid CRMP2-derived peptide that, when fused to the tat transduction domain of HIV-1, inhibited Ca influx in dorsal root ganglion neurons. This peptide mimics the negative regulation of CRMP2 activity by neurofibromin. Neurons treated with tat-CRMP2/neurofibromin regulating peptide 1 (t-CNRP1) exhibited a decreased Cav2.2 membrane localization, and uncoup...Continue Reading

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Citations

Apr 19, 2018·Expert Opinion on Therapeutic Targets·James A Walker, M Upadhyaya
Aug 25, 2017·Channels·Aubin MoutalRajesh Khanna
Mar 28, 2019·Molecular Neurobiology·Aubin MoutalRajesh Khanna
Dec 20, 2018·Molecular Neurobiology·Jie YuRajesh Khanna
Oct 27, 2018·Neuronal Signaling·Lindsey A Chew, Rajesh Khanna
Nov 5, 2019·Channels·Aubin MoutalRajesh Khanna
Aug 11, 2020·Pain·Kimberly GomezRajesh Khanna
Apr 16, 2018·Neuroscience·Aubin MoutalRajesh Khanna

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