DPYSL2

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DPYSL2

A gene on chromosome 8p22-p21 that encodes a member of the collapsin response mediator protein family, which forms homo- and heterotetramers. DPYSL2 plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration.  

Molecular pathology
DPYSL2 has been implicated in multiple neurological disorders; hyperphosphorylation of the encoded protein may play a role in the development of Alzheimer's disease.
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Kawano et al., "Phosphorylation by rho kinase regulates CRMP-2 activity in growth cones," Molecular and Cellular Biology, vol.
Kaibuchi, "GSK-3[beta] regulates phosphorylation of CRMP-2 and neuronal polarity," Cell, vol.
PKC appears to also trigger a RhoA-activating cascade through downstream Rho-associated protein kinase (ROCK), which subsequently phosphorylates the collapsin response mediator protein 2 (CRMP-2) and causes growth cone collapse [127] (Figure 2).
In another study in patients with MTLE associated with hippocampal sclerosis a decreased level of the collapsin response mediated protein-2 (CRMP-2) was reported [128].
One of the specific substrates that our group has recently defined is CRMP-2 (Figure 3).
It has been hypothesised that GSK-3 overactivity may potentiate sporadic and familial forms of AD by enhancing tau hyperphosphorylation [84] and APP processing and possibly through the phosphorylation of CRMP-2 leading to profound memory impairment [81] (Figures 2 and 3).
According to the company Web site, lacosamide has a novel dual method of action, selectively enhancing slow inactivation of voltage-gated sodium channels, and modulating collapsin response mediator protein 2 (CRMP-2).
It selectively enhances slow inactivation of sodium channels and interacts with the neuroplasticity-relevant target - collapsin-response mediator protein-2 (CRMP-2).
Kimura et al., "CRMP-2 binds to tubulin heterodimers to promote microtubule assembly," Nature Cell Biology, vol.
Khanna et al., "CRMP-2 peptide mediated decrease of high and low voltage-activated calcium channels, attenuation of nociceptor excitability, and anti-nociception in a model of AIDS therapy-induced painful peripheral neuropathy," Molecular Pain, vol.
Li, "GSK-3alpha/beta- mediated phosphorylation of CRMP-2 regulates activity-dependent dendritic growth," Journal of Neurochemistry, vol.
Wilson et al., "Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic [Ca.sup.2+] channel complex," Nature Medicine, vol.