Collapsin-Induced Growth Cone Collapse Mediated by an Intracellular Protein Related to Unc-33
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). "
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
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- "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) "
ABSTRACT: The biological characteristics of rooster sperm that has undergone freezing treatment remain elusive. This study analyzed the change in sperm proteins after freezing-thawing treatment by using a proteomic approach. Semen from three 36-wk-old L2 strain Taiwan country chickens were used. A qualifying ejaculate containing more than 80% motility and volume 200μL was used for cryopreservation. The proteomic analysis explored 55 protein spots that differed significantly before and after freezing-thawing treatment (P<0.05). Among the 55 protein spots, expression levels of 19 proteins decreased after treatment. Forty-five differentially expressed protein spots were identified and belong to 33 proteins. Results of gene ontology analysis revealed that most differentially expressed proteins were involved in molecular function of the cellular metabolism process (28%) and cellular carbohydrate metabolism process (15%), and were associated with molecular function of oxidoreductase activity (19%) and protein binding (18%). The differentially expressed proteins before and after freezing-thawing treatment, including fructose-bisphosphate aldolase C, triosephosphate isomerase, aconitate hydratase, tubulin and outer dense-fiber protein, are associated with sperm energy metabolism and flagellum structure. In conclusion, freezing-thawing treatment significantly affects the expression of proteins related to sperm metabolism and structure in chicken spermatozoa. The differing levels of these proteins could be valuable for further enhancing the fertility of frozen-thawed chicken spermatozoa. Copyright © 2014 Elsevier B.V. All rights reserved.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). "
ABSTRACT: Aberrant ion channel function has been heralded as a main underlying mechanism driving epilepsy and its symptoms. However, it has become increasingly clear that treatment strategies targeting voltage-gated sodium or calcium channels merely mask the symptoms of epilepsy without providing disease-modifying benefits. Ion channel function is likely only one important cog in a highly complex machine. Gross morphological changes, such as reactive sprouting and outgrowth, may also play a role in epileptogenesis. Mechanisms responsible for these changes are not well-understood. Here we investigate the potential involvement of the neurite outgrowth-promoting molecule collapsin response mediator protein 2 (CRMP2). CRMP2 activity, in this respect, is regulated by phosphorylation state, where phosphorylation by a variety of kinases, including glycogen synthase kinase 3 β (GSK3β) renders it inactive. Phosphorylation (inactivation) of CRMP2 was decreased at two distinct phases following traumatic brain injury (TBI). While reduced CRMP2 phosphorylation during the early phase was attributed to the inactivation of GSK3β, the sustained decrease in CRMP2 phosphorylation in the late phase appeared to be independent of GSK3β activity. Instead, the reduction in GSK3β-phosphorylated CRMP2 was attributed to a loss of priming by cyclin-dependent kinase 5 (CDK5), which allows for subsequent phosphorylation by GSK3β. Based on the observation that the proportion of active CRMP2 is increased for up to 4 weeks following TBI, it was hypothesized that it may drive neurite outgrowth, and therefore, circuit reorganization during this time. Therefore, a novel small-molecule tool was used to target CRMP2 in an attempt to determine its importance in mossy fiber sprouting following TBI. In this report, we demonstrate novel differential regulation of CRMP2 phosphorylation by GSK3β and CDK5 following TBI.Frontiers in Cellular Neuroscience 05/2014; 8:135. DOI:10.3389/fncel.2014.00135 · 4.18 Impact Factor