The vesicle protein SAM-4 regulates the processivity of synaptic vesicle transport
| Autor: | Tim Mahoney, Shikha Ahlawat, Sandhya P. Koushika, Michael L. Nonet, Qun Zheng, Anneliese M. Schaefer |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Neural Homeostasis medicine.disease_cause Axonal Transport Nervous System Mechanical Treatment of Specimens Animals Genetically Modified 0302 clinical medicine Neurobiology of Disease and Regeneration 11. Sustainability Medicine and Health Sciences Genetics (clinical) KIF1A Neurons Genetics 0303 health sciences Mutation Cell biology Electroporation Neurology Specimen Disruption Intercellular Signaling Peptides and Proteins Synaptic vesicle transport Synaptic Vesicles Anatomy Research Article lcsh:QH426-470 Protein domain Nerve Tissue Proteins Biology Research and Analysis Methods Synaptic vesicle Motor protein 03 medical and health sciences Neurites medicine Animals Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Binding Sites Membrane Proteins Biology and Life Sciences Processivity Phosphoproteins Motor System lcsh:Genetics Specimen Preparation and Treatment Axoplasmic transport 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | PLoS Genetics, Vol 10, Iss 10, p e1004644 (2014) PLoS Genetics |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Axonal transport of synaptic vesicles (SVs) is a KIF1A/UNC-104 mediated process critical for synapse development and maintenance yet little is known of how SV transport is regulated. Using C. elegans as an in vivo model, we identified SAM-4 as a novel conserved vesicular component regulating SV transport. Processivity, but not velocity, of SV transport was reduced in sam-4 mutants. sam-4 displayed strong genetic interactions with mutations in the cargo binding but not the motor domain of unc-104. Gain-of-function mutations in the unc-104 motor domain, identified in this study, suppress the sam-4 defects by increasing processivity of the SV transport. Genetic analyses suggest that SAM-4, SYD-2/liprin-α and the KIF1A/UNC-104 motor function in the same pathway to regulate SV transport. Our data support a model in which the SV protein SAM-4 regulates the processivity of SV transport. Author Summary Most cellular components of neurons are synthesized in the cell body and must be transported great distances to form synapses at the ends of axons and dendrites. Neurons use a specialized axonal transport system consisting of microtubule cytoskeletal tracks and numerous molecular motors to shuttle specific cargo to specific destinations in the cell. Disruption of this transport system has severe consequences to human health. Disruption of specific neuronal motors are linked to hereditary neurodegenerative conditions including forms of Charcot Marie Tooth disease, several types of hereditary spastic paraplegia, and certain forms of amyotrophic lateral sclerosis motor neuron disease. Despite recent progress in defining the cargo of many of kinesin family motors in neurons, little is known about how the activity of these transport systems is regulated. Here, using a simple invertebrate model we identify and characterize a novel protein that regulates the efficacy of the KIF1A motor that mediates transport of synaptic vesicles. These studies define a new pathway regulating SV transport with potential links to human neurological disease. |
| Databáze: | OpenAIRE |
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