Collapsin-Induced Growth Cone Collapse Mediated by an Intracellular Protein Related to Unc-33

Yale University, New Haven, Connecticut, United States
Nature (Impact Factor: 42.35). 09/1995; 376(6540):509-14. DOI: 10.1038/376509a0
Source: PubMed

ABSTRACT 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.

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    • "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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    ABSTRACT: Assemblies of huntingtin (HTT) fragments with expanded polyglutamine (polyQ) tracts are a pathological hallmark of Huntington's disease (HD). The molecular mechanisms by which these structures are formed and cause neuronal dysfunction and toxicity are poorly understood. Here, we utilized available gene expression data sets of selected brain regions of HD patients and controls for systematic interaction network filtering in order to predict disease-relevant, brain region-specific HTT interaction partners. Starting from a large protein-protein interaction (PPI) data set, a step-by-step computational filtering strategy facilitated the generation of a focused PPI network that directly or indirectly connects 13 proteins potentially dysregulated in HD with the disease protein HTT. This network enabled the discovery of the neuron-specific protein CRMP1 that targets aggregation-prone, N-terminal HTT fragments and suppresses their spontaneous self-assembly into proteotoxic structures in various models of HD. Experimental validation indicates that our network filtering procedure provides a simple but powerful strategy to identify disease-relevant proteins that influence misfolding and aggregation of polyQ disease proteins. © 2015 Stroedicke et al.; Published by Cold Spring Harbor Laboratory Press.
    Genome Research 04/2015; 25(5). DOI:10.1101/gr.182444.114 · 13.85 Impact Factor
    • "Tubulin beta-3 chain 1.74, 2.96 Kazuo (2011) Tubulin alpha-3/alpha-7 chain 2.61 Tektin 2 −2.18 Nojima et al. (1995) Tektin 5 1.57 Outer dense fiber protein 2.83 Pixton et al. (2004) Others Voltage-dependent anion-selective channel protein 2 1.50 Liu et al. (2010) Heat shock protein 70 2.86 Naaby-Hansen and Herr (2010) Superoxide dismutase −1.74 Tuncer et al. (2011) Dihydropyrimidinase −2.33, 1.94 Goshima et al. (1995) "
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    Animal Reproduction Science 12/2014; 152. DOI:10.1016/j.anireprosci.2014.11.011 · 1.58 Impact Factor
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    • "Given CRMP2's remarkable ability to regulate ion channel function, it can be at times difficult to consider its many other functions, particularly those for which it was first identified (i.e., neurite outgrowth and guidance) (Goshima et al., 1995). Importantly, of the myriad of CRMP2 functions, it is the ability to promote neurite outgrowth that is impacted by (R)-LCM, not those associated with ion channel function (Wang and Khanna, 2011; Wilson et al., 2012b). "
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