1. Developmental changes in trak-mediated mitochondrial transport in neurons
- Author
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Loss, Omar and Stephenson, F. Anne
- Subjects
DIV, days in vitro ,Trafficking kinesin binding protein ,PBS, phosphate-buffered saline ,Synaptophysin ,TRAK ,Nerve Tissue Proteins ,tau Proteins ,MAP, microtubule-associated protein 2 ,N-Acetylglucosaminyltransferases ,Transfection ,Axonal Transport ,Hippocampus ,Article ,Cellular and Molecular Neuroscience ,Animals ,Humans ,RNA, Small Interfering ,Molecular Biology ,PSD-95, postsynaptic density protein 95 ,scrRNA, scrambled RNA ,Cells, Cultured ,Mitochondrial transport ,Cerebral Cortex ,Neurons ,Microscopy, Confocal ,Intracellular Signaling Peptides and Proteins ,Membrane Proteins ,Kinesin ,Dendrites ,Cell Biology ,EGFP, enhanced green fluorescent protein ,Mitochondria ,Rats ,Adaptor Proteins, Vesicular Transport ,nervous system ,shRNA, short hairpin RNA ,FITC, fluorescein isothiocyanate ,Carrier Proteins ,DsRed, discosoma red fluorescent protein ,Disks Large Homolog 4 Protein ,DAPI, 4′,6-diamidino-2-phenylindole - Abstract
Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. A recent report suggested that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons whereas TRAK2 controls mitochondrial transport in dendrites. However, it is not clear whether the function of any of these proteins is exclusive to axons or dendrites and if their mechanisms of action are conserved between different neuronal populations and also, during maturation. Here, a comparative study was carried out into TRAK-mediated mitochondrial mobility in axons and dendrites of hippocampal and cortical neurons during maturation in vitro using a shRNA gene knockdown approach. It was found that in mature hippocampal and cortical neurons, TRAK1 predominantly mediates axonal mitochondrial transport whereas dendritic transport is mediated via TRAK2. In young, maturing neurons, TRAK1 and TRAK2 contribute similarly in mitochondrial transport in both axons and dendrites in both neuronal types. These findings demonstrate maturation regulation of mitochondrial transport which is conserved between at least two distinct neuronal subtypes., Graphical abstract Image 1, Highlights • Mitochondrial transport and velocity changes during neuronal maturation. • TRAK1 and TRAK2 contribute to transport in axons and dendrites of immature neurons. • In mature neurons TRAK1 controls axonal mitochondrial transport. • In mature neurons TRAK2 controls dendritic mitochondrial transport.
- Published
- 2017
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