CRMP2

2022-09-10

CRMP2 (Collapsin response mediator protein-2) #

• Part of Axon Guidance.
• Phosphorylated (deactivated) by kinases like GSK-3β (Thr-509, Thr-514, Ser-518), CDK5, ROCK (Thr-555) via lowering binding affinity to Tubulin and Numb.
• Expression induced by GDNF. Increased CRMP2 = microtubule stabilization and enhanced neurite outgrowth
• Some Cav2.2/CDK5 stuff going on https://www.researchgate.net/figure/Regulation-of-voltage-gated-calcium-channel-CaV22-and-voltagegated-sodium-channel-NaV17_fig2_332052935
• CRMP2 Is Involved in Regulation of Mitochondrial Morphology and Motility in Neurons
  • Deletion of CRMP2 with a small interfering RNA (siRNA) resulted in increased mitochondrial fission and diminished mitochondrial traffic.
  • Attached to neuronal mitochondria. Binds to Drp1, Miro 2, and Kinesin light chain 1 (KLC1).
  • PP1+PP2A inhibition resulted in increased CRMP2 phosphorylation at Thr509/514, Ser522, and Thr555, and augmented Drp1 phosphorylation at Ser616. The CRMP2-binding small molecule (S)-lacosamide ((S)-LCM) prevented an OA-induced increase in CRMP2 phosphorylation at Thr509/514 and Ser522 but not at Thr555, and also failed to alleviate Drp1 phosphorylation
    • The increased CRMP2 phosphorylation correlated with decreased CRMP2 binding to Drp1, Miro 2, and KLC1.
• Collapsin Response Mediator Protein-2 (CRMP2) is a Plausible Etiological Factor and Potential Therapeutic Target in Alzheimer’s Disease: Comparison and Contrast with Microtubule-Associated Protein Tau (2016):
  • It is suspected CRMP2 in AD is sequestered into nascent NFTs.
• Collapsin Response Mediator Proteins: Novel targets for Alzheimer’s disease (Oct 2020)
  • NMDA->CDK5 deactivating. Hmm.
  • AD sees hyperphosphorylation of CRMP2; Deleting the Cdk5 phosphorylation site of CRMP2 prevented impairments in LTP and memory formation induced by Aβ25–35 oligomers.