Collapsin, a member of the newly recognized semaphorin family, contributes to axonal pathfinding during neural development by inhibiting growth cone extension. The mechanism of collapsin action is poorly understood. Here we use a Xenopus laevis oocyte expression system to identify molecules involved in collapsin signalling, because several experiments have raised the possibility that heterotrimeric GTP-binding proteins might participate in these events. A collapsin response mediator protein of relative molecular mass (M(r)) 62K (CRMP-62) required for collapsin-induced inward currents in X. laevis oocytes is isolated. CRMP-62 shares homology with UNC-33, a nematode neuronal protein required for appropriately directed axonal extension. CRMP-62 is localized exclusively in the developing chick nervous system. Introduction of anti-CRMP-62 antibodies into dorsal root ganglion neurons blocks collapsin-induced growth cone collapse. CRMP-62 appears to be an intracellular component of a signalling cascade initiated by an unidentified transmembrane collapsin-binding protein.
"The formation, maturation, and maintenance of dendritic spines are tightly regulated by different extracellular signals including semaphorin 3A (Sema3A). Collapsin response mediator proteins (CRMPs), initially identified as a signaling molecule of Sema3A , are composed of five homologous cytosolic phosphoproteins (CRMP1–5) and are highly expressed in developing and adult nervous systems    . CRMPs bind with tubulin heterodimers, whereas the sequential phosphorylation of CRMPs lowers their binding affinity to tubulin . "
[Show abstract][Hide abstract] ABSTRACT: Proper density and morphology of dendritic spines are important for higher brain functions such as learning and memory. However, our knowledge about molecular mechanisms that regulate the development and maintenance of dendritic spines is limited. We recently reported that cyclin-dependent kinase 5 (Cdk5) is required for the development and maintenance of dendritic spines of cortical neurons in the mouse brain. Previous in vitro studies have suggested the involvement of Cdk5 substrates in the formation of dendritic spines; however, their role in spine development has not been tested in vivo. Here, we demonstrate that Cdk5 phosphorylates collapsin response mediator protein 2 (CRMP2) in the dendritic spines of cultured hippocampal neurons and in vivo in the mouse brain. When we eliminated CRMP2 phosphorylation in CRMP2 KI/KI mice, the densities of dendritic spines significantly decreased in hippocampal CA1 pyramidal neurons in the mouse brain. These results indicate that phosphorylation of CRMP2 by Cdk5 is important for dendritic spine development in cortical neurons in the mouse hippocampus.
"For more detailed experimental validation studies, we focused our efforts on the protein CRMP1, whose transcript levels are significantly diminished in HD brains (Fig. 1B). CRMP1 is a cytoplasmic phosphoprotein that is predominantly expressed in neurons (Goshima et al. 1995). Previous studies revealed that mice lacking CRMP1 show impairment of learning and memory (Su et al. 2007), suggesting that a reduction of CRMP1 levels in HD brains might contribute to the disease phenotype (Paulsen et al. 2013). "
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