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

Yale University, New Haven, Connecticut, United States
Nature (Impact Factor: 41.46). 09/1995; 376(6540):509-14. DOI: 10.1038/376509a0
Source: PubMed


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.

1 Follower
5 Reads
  • Source
    • "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 [1], are composed of five homologous cytosolic phosphoproteins (CRMP1–5) and are highly expressed in developing and adult nervous systems [2] [3] [4] [5]. CRMPs bind with tubulin heterodimers, whereas the sequential phosphorylation of CRMPs lowers their binding affinity to tubulin [6]. "
    [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.
    Neural Plasticity 07/2015; · 3.60 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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 · 14.63 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) "
    [Show abstract] [Hide abstract]
    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 · 1.51 Impact Factor
Show more