The Experts below are selected from a list of 192 Experts worldwide ranked by ideXlab platform

Sheridan L. Swope - One of the best experts on this subject based on the ideXlab platform.

  • Identification of a dynein Molecular Motor component in Torpedo electroplax; binding and phosphorylation of Tctex‐1 by Fyn
    FEBS Letters, 1998
    Co-Authors: Tao Mou, Jonathan R. Kraas, Eric T. Fung, Sheridan L. Swope
    Abstract:

    The microtubule Protein Tctex-1 was cloned from Torpedo electroplax, a biochemical model of the neuromuscular junction, using the unique domain of Fyn in the yeast two hybrid system. Binding of Tctex-1 and Fyn also occurred in vitro. Torpedo Tctex-1 was contained within the Molecular Motor Protein dynein. A Src class kinase was also complexed with dynein. Tctex-1 was enriched in electric organ vs. skeletal muscle, was present in the postsynaptic membrane, and coprecipitated with the acetylcholine receptor. The sequence of Tctex-1 contained a tyrosine phosphorylation motif and Tctex-1 could be phosphorylated by Fyn in vitro and in vivo. These data demonstrated that Tctex-1-containing dynein is a cytoskeletal element at the acetylcholine receptor-enriched postsynaptic membrane and suggested that Tctex-1 may be a substrate for Fyn.

  • Identification of a dynein Molecular Motor component in Torpedo electroplax; binding and phosphorylation of Tctex-1 by Fyn.
    FEBS letters, 1998
    Co-Authors: Tao Mou, Jonathan R. Kraas, Eric T. Fung, Sheridan L. Swope
    Abstract:

    The microtubule Protein Tctex-1 was cloned from Torpedo electroplax, a biochemical model of the neuromuscular junction, using the unique domain of Fyn in the yeast two hybrid system. Binding of Tctex-1 and Fyn also occurred in vitro. Torpedo Tctex-1 was contained within the Molecular Motor Protein dynein. A Src class kinase was also complexed with dynein. Tctex-1 was enriched in electric organ vs. skeletal muscle, was present in the postsynaptic membrane, and coprecipitated with the acetylcholine receptor. The sequence of Tctex-1 contained a tyrosine phosphorylation motif and Tctex-1 could be phosphorylated by Fyn in vitro and in vivo. These data demonstrated that Tctex-1-containing dynein is a cytoskeletal element at the acetylcholine receptor-enriched postsynaptic membrane and suggested that Tctex-1 may be a substrate for Fyn.

Tao Mou - One of the best experts on this subject based on the ideXlab platform.

  • Identification of a dynein Molecular Motor component in Torpedo electroplax; binding and phosphorylation of Tctex‐1 by Fyn
    FEBS Letters, 1998
    Co-Authors: Tao Mou, Jonathan R. Kraas, Eric T. Fung, Sheridan L. Swope
    Abstract:

    The microtubule Protein Tctex-1 was cloned from Torpedo electroplax, a biochemical model of the neuromuscular junction, using the unique domain of Fyn in the yeast two hybrid system. Binding of Tctex-1 and Fyn also occurred in vitro. Torpedo Tctex-1 was contained within the Molecular Motor Protein dynein. A Src class kinase was also complexed with dynein. Tctex-1 was enriched in electric organ vs. skeletal muscle, was present in the postsynaptic membrane, and coprecipitated with the acetylcholine receptor. The sequence of Tctex-1 contained a tyrosine phosphorylation motif and Tctex-1 could be phosphorylated by Fyn in vitro and in vivo. These data demonstrated that Tctex-1-containing dynein is a cytoskeletal element at the acetylcholine receptor-enriched postsynaptic membrane and suggested that Tctex-1 may be a substrate for Fyn.

  • Identification of a dynein Molecular Motor component in Torpedo electroplax; binding and phosphorylation of Tctex-1 by Fyn.
    FEBS letters, 1998
    Co-Authors: Tao Mou, Jonathan R. Kraas, Eric T. Fung, Sheridan L. Swope
    Abstract:

    The microtubule Protein Tctex-1 was cloned from Torpedo electroplax, a biochemical model of the neuromuscular junction, using the unique domain of Fyn in the yeast two hybrid system. Binding of Tctex-1 and Fyn also occurred in vitro. Torpedo Tctex-1 was contained within the Molecular Motor Protein dynein. A Src class kinase was also complexed with dynein. Tctex-1 was enriched in electric organ vs. skeletal muscle, was present in the postsynaptic membrane, and coprecipitated with the acetylcholine receptor. The sequence of Tctex-1 contained a tyrosine phosphorylation motif and Tctex-1 could be phosphorylated by Fyn in vitro and in vivo. These data demonstrated that Tctex-1-containing dynein is a cytoskeletal element at the acetylcholine receptor-enriched postsynaptic membrane and suggested that Tctex-1 may be a substrate for Fyn.

Valérie Bercier - One of the best experts on this subject based on the ideXlab platform.

  • Dynactin1 depletion leads to neuromuscular synapse instability and functional abnormalities.
    Molecular Neurodegeneration, 2019
    Co-Authors: Valérie Bercier, Jeffrey M. Hubbard, Kevin Fidelin, Karine Duroure, Céline Revenu, Claire Wyart, Thomas O. Auer, Filippo Del Bene
    Abstract:

    Dynactin subunit 1 is the largest subunit of the dynactin complex, an activator of the Molecular Motor Protein complex dynein. Reduced levels of DCTN1 mRNA and Protein have been found in sporadic amyotrophic lateral sclerosis (ALS) patients, and mutations have been associated with disease, but the role of this Protein in disease pathogenesis is still unknown. We characterized a Dynactin1a depletion model in the zebrafish embryo and combined in vivo Molecular analysis of primary Motor neuron development with live in vivo axonal transport assays in single cells to investigate ALS-related defects. To probe neuromuscular junction (NMJ) function and organization we performed paired Motor neuron-muscle electrophysiological recordings and GCaMP calcium imaging in live, intact larvae, and the synapse structure was investigated by electron microscopy. Here we show that Dynactin1a depletion is sufficient to induce defects in the development of spinal cord Motor neurons and in the function of the NMJ. We observe synapse instability, impaired growth of primary Motor neurons, and higher failure rates of action potentials at the NMJ. In addition, the embryos display locomotion defects consistent with NMJ dysfunction. Rescue of the observed phenotype by overexpression of wild-type human DCTN1-GFP indicates a cell-autonomous mechanism. Synaptic accumulation of DCTN1-GFP, as well as ultrastructural analysis of NMJ synapses exhibiting wider synaptic clefts, support a local role for Dynactin1a in synaptic function. Furthermore, live in vivo analysis of axonal transport and cytoskeleton dynamics in primary Motor neurons show that the phenotype reported here is independent of modulation of these processes. Our study reveals a novel role for Dynactin1 in ALS pathogenesis, where it acts cell-autonomously to promote Motor neuron synapse stability independently of dynein-mediated axonal transport.

  • Dynactin1 depletion leads to neuromuscular synapse instability and functional abnormalities
    Molecular Neurodegeneration, 2019
    Co-Authors: Valérie Bercier, Kevin Fidelin, Karine Duroure, Céline Revenu, Claire Wyart, Jeffrey Hubbard, Thomas Auer, Filippo Del Bene
    Abstract:

    BACKGROUND: Dynactin subunit 1 is the largest subunit of the dynactin complex, an activator of the Molecular Motor Protein complex dynein. Reduced levels of DCTN1 mRNA and Protein have been found in sporadic amyotrophic lateral sclerosis (ALS) patients, and mutations have been associated with disease, but the role of this Protein in disease pathogenesis is still unknown. METHODS: We characterized a Dynactin1a depletion model in the zebrafish embryo and combined in vivo Molecular analysis of primary Motor neuron development with live in vivo axonal transport assays in single cells to investigate ALS-related defects. To probe neuromuscular junction (NMJ) function and organization we performed paired Motor neuron-muscle electrophysiological recordings and GCaMP calcium imaging in live, intact larvae, and the synapse structure was investigated by electron microscopy. RESULTS: Here we show that Dynactin1a depletion is sufficient to induce defects in the development of spinal cord Motor neurons and in the function of the NMJ. We observe synapse instability, impaired growth of primary Motor neurons, and higher failure rates of action potentials at the NMJ. In addition, the embryos display locomotion defects consistent with NMJ dysfunction. Rescue of the observed phenotype by overexpression of wild-type human DCTN1-GFP indicates a cell-autonomous mechanism. Synaptic accumulation of DCTN1-GFP, as well as ultrastructural analysis of NMJ synapses exhibiting wider synaptic clefts, support a local role for Dynactin1a in synaptic function. Furthermore, live in vivo analysis of axonal transport and cytoskeleton dynamics in primary Motor neurons show that the phenotype reported here is independent of modulation of these processes. CONCLUSIONS: Our study reveals a novel role for Dynactin1 in ALS pathogenesis, where it acts cell-autonomously to promote Motor neuron synapse stability independently of dynein-mediated axonal transport.

Linda Hassinger - One of the best experts on this subject based on the ideXlab platform.

  • myosin va binding to neurofilaments is essential for correct myosin va distribution and transport and neurofilament density
    Journal of Cell Biology, 2002
    Co-Authors: Mala V Rao, Linda J Engle, Panaiyur S Mohan, Aidong Yuan, Dike Qiu, Anne M Cataldo, Linda Hassinger
    Abstract:

    The identification of Molecular Motors that modulate the neuronal cytoskeleton has been elusive. Here, we show that a Molecular Motor Protein, myosin Va, is present in high proportions in the cytoskeleton of mouse CNS and peripheral nerves. Immunoelectron microscopy, coimmunoprecipitation, and blot overlay analyses demonstrate that myosin Va in axons associates with neurofilaments, and that the NF-L subunit is its major ligand. A physiological association is indicated by observations that the level of myosin Va is reduced in axons of NF-L–null mice lacking neurofilaments and increased in mice overexpressing NF-L, but unchanged in NF-H–null mice. In vivo pulse-labeled myosin Va advances along axons at slow transport rates overlapping with those of neurofilament Proteins and actin, both of which coimmunoprecipitate with myosin Va. Eliminating neurofilaments from mice selectively accelerates myosin Va translocation and redistributes myosin Va to the actin-rich subaxolemma and membranous organelles. Finally, peripheral axons of dilute-lethal mice, lacking functional myosin Va, display selectively increased neurofilament number and levels of neurofilament Proteins without altering axon caliber. These results identify myosin Va as a neurofilament-associated Protein, and show that this association is essential to establish the normal distribution, axonal transport, and content of myosin Va, and the proper numbers of neurofilaments in axons.

Jonathan R. Kraas - One of the best experts on this subject based on the ideXlab platform.

  • Identification of a dynein Molecular Motor component in Torpedo electroplax; binding and phosphorylation of Tctex‐1 by Fyn
    FEBS Letters, 1998
    Co-Authors: Tao Mou, Jonathan R. Kraas, Eric T. Fung, Sheridan L. Swope
    Abstract:

    The microtubule Protein Tctex-1 was cloned from Torpedo electroplax, a biochemical model of the neuromuscular junction, using the unique domain of Fyn in the yeast two hybrid system. Binding of Tctex-1 and Fyn also occurred in vitro. Torpedo Tctex-1 was contained within the Molecular Motor Protein dynein. A Src class kinase was also complexed with dynein. Tctex-1 was enriched in electric organ vs. skeletal muscle, was present in the postsynaptic membrane, and coprecipitated with the acetylcholine receptor. The sequence of Tctex-1 contained a tyrosine phosphorylation motif and Tctex-1 could be phosphorylated by Fyn in vitro and in vivo. These data demonstrated that Tctex-1-containing dynein is a cytoskeletal element at the acetylcholine receptor-enriched postsynaptic membrane and suggested that Tctex-1 may be a substrate for Fyn.

  • Identification of a dynein Molecular Motor component in Torpedo electroplax; binding and phosphorylation of Tctex-1 by Fyn.
    FEBS letters, 1998
    Co-Authors: Tao Mou, Jonathan R. Kraas, Eric T. Fung, Sheridan L. Swope
    Abstract:

    The microtubule Protein Tctex-1 was cloned from Torpedo electroplax, a biochemical model of the neuromuscular junction, using the unique domain of Fyn in the yeast two hybrid system. Binding of Tctex-1 and Fyn also occurred in vitro. Torpedo Tctex-1 was contained within the Molecular Motor Protein dynein. A Src class kinase was also complexed with dynein. Tctex-1 was enriched in electric organ vs. skeletal muscle, was present in the postsynaptic membrane, and coprecipitated with the acetylcholine receptor. The sequence of Tctex-1 contained a tyrosine phosphorylation motif and Tctex-1 could be phosphorylated by Fyn in vitro and in vivo. These data demonstrated that Tctex-1-containing dynein is a cytoskeletal element at the acetylcholine receptor-enriched postsynaptic membrane and suggested that Tctex-1 may be a substrate for Fyn.