title: Developmental changes in trak-mediated mitochondrial transport in neurons.
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.
authors.affiliation: School of Pharmacy University College London, 29/39 Brunswick Square, London WC1N 1AX, United Kingdom.
authors.forename: Omar
authors.initials: O
authors.lastname: Loss
authors.affiliation: School of Pharmacy University College London, 29/39 Brunswick Square, London WC1N 1AX, United Kingdom. Electronic address: anne.stephenson@ucl.ac.uk.
authors.forename: F Anne
authors.initials: FA
authors.lastname: Stephenson
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001370:Axonal Transport / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003712:Dendrites / Q000235:genetics; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016708:Synaptophysin / Q000378:metabolism; D014162:Transfection; D016875:tau Proteins / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D016708:Synaptophysin; C531552:TRAK1 protein, human; C465341:TRAK2 protein, human; D016875:tau Proteins; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase
keywords: Axonal transport; Kinesin; Mitochondrial transport; TRAK; Trafficking kinesin binding protein