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
Neurochemical evidence for the involvement of N-type calcium channels in transmitter secretion from peripheral endings of sensory nerves in guinea pigs
A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations
Inhibition of neurotransmission by peptides containing the synaptic protein interaction site of N-type Ca2+ channels
Interactions between presynaptic calcium channels and proteins implicated in synaptic vesicle trafficking and exocytosis
Selective peptide antagonist of the class E calcium channel from the venom of the tarantula Hysterocrates gigas
Vesicle-associated proteins and P2X receptor clusters at single sympathetic varicosities in mouse vas deferens
N- and L- but not P/Q-type calcium channels contribute to neuropeptide release from rat skin in vitro
Residue Gly1326 of the N-type calcium channel alpha 1B subunit controls reversibility of omega-conotoxin GVIA and MVIIA block
Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel
Deletion of the synaptic protein interaction site of the N-type (CaV2.2) calcium channel inhibits secretion in mouse pheochromocytoma cells
Stimulus-evoked release of neuropeptides is enhanced in sensory neurons from mice with a heterozygous mutation of the Nf1 gene
Neurofibromatosis type 1 (NF1) tumor suppressor, neurofibromin, regulates the neuronal differentiation of PC12 cells via its associating protein, CRMP-2
Differential block of sensory neuronal voltage-gated sodium channels by lacosamide [(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide], lidocaine, and carbamazepine
Autoregulation in PC12 cells via P2Y receptors: Evidence for non-exocytotic nucleotide release from neuroendocrine cells
Time course and specificity of the pharmacological disruption of the trafficking of voltage-gated calcium channels by gabapentin
Roles of calcitonin gene-related peptide and its receptors in pain-related behavioral responses in the central nervous system
An atypical role for collapsin response mediator protein 2 (CRMP-2) in neurotransmitter release via interaction with presynaptic voltage-gated calcium channels
Regulation of N-type voltage-gated calcium channels (Cav2.2) and transmitter release by collapsin response mediator protein-2 (CRMP-2) in sensory neurons
Augmented sodium currents contribute to the enhanced excitability of small diameter capsaicin-sensitive sensory neurons isolated from Nf1+/⁻ mice
In silico docking and electrophysiological characterization of lacosamide binding sites on collapsin response mediator protein-2 identifies a pocket important in modulating sodium channel slow inactivation.
Experiences of families with a child, adolescent, or young adult with neurofibromatosis type 1 and plexiform neurofibroma evaluated for clinical trials participation at the National Cancer Institute
Ras signaling pathways mediate NGF-induced enhancement of excitability of small-diameter capsaicin-sensitive sensory neurons from wildtype but not Nf1+/- mice
Betulinic acid, derived from the desert lavender Hyptis emoryi, attenuates paclitaxel-, HIV-, and nerve injury-associated peripheral sensory neuropathy via block of N- and T-type calcium channels
AAV-encoded CaV 2.2 peptide aptamer CBD3A6K for primary sensory neuron-targeted treatment of established neuropathic pain
Targeting the CaVα-CaVβ interaction yields an antagonist of the N-type CaV2.2 channel with broad antinociceptive efficacy.
Nasal delivery of a CRMP2-derived CBD3 adenovirus improves cognitive function and pathology in APP/PS1 transgenic mice.
Targeted disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels
Dynamic CRMP2 Regulation of CaV2.2 in the Prefrontal Cortex Contributes to the Reinstatement of Cocaine Seeking
Neuronal Conditional Knockout of Collapsin Response Mediator Protein 2 Ameliorates Disease Severity in a Mouse Model of Multiple Sclerosis
Towards a neurobiological understanding of pain in neurofibromatosis type 1: mechanisms and implications for treatment
Studies on CRMP2 SUMOylation-deficient transgenic mice identify sex-specific Nav1.7 regulation in the pathogenesis of chronic neuropathic pain.
Calcium & Bioenergetics
Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.