Lanthionine ketimine ethyl ester partially rescues neurodevelopmental defects in unc-33 (DPYSL2/CRMP2) mutants.

摘要: Lanthionine ketimine (LK) is a natural sulfur amino acid metabolite with potent neurotrophic activity. Proteomics indicate that LK interacts collapsin response mediator protein-2 (CRMP2/DPYSL2/UNC-33), brain-enriched protein was shown to regulate cytoskeletal remodeling, neuronal morphology, and synaptic function. To elucidate further the molecular interplay biological action of UNC-33, we began examining nervous system Caenorhabditis elegans nematodes in which both concentrations UNC-33 were manipulated. this end, cell-permeable LK-ester (LKE) administered developing C. engineered express yellow fluorescent (YFP) cholinergic neurons (strain RM3128) or green (GFP) GABAergic CZ1200), neural morphology assessed. Fluorescent imaging analyses show LKE exposure wild-type animals induced commissure outgrowth, crossing over, bundling neurites from motor neurons. Additionally, when unc-33(e204) hypomorph mutant (D389N substitution mutants) exposed LKE, neuroanatomical defects incomplete dorsoventral commissures ventral nerve cord gaps partially rescued. In contrast, did not rescue found unc-33(mn407) null mutant. Together these data suggest possible functions for as regulator neuritic elongation, corroborate roles UNC-33/CRMP2 mechanism activity, potential therapeutic molecule neurological diseases involving CRMP2 dysfunction.