Axonal transport of mitochondria to synapses depends on milton, a novel Drosophila protein.
A protein required to localize mitochondria to Drosophila nerve terminals has been identified genetically. Photoreceptors mutant for milton show aberrant synaptic transmission despite normal phototransduction. Without Milton, synaptic terminals and axons lack mitochondria, although mitochondria are numerous in neuronal cell bodies. In contrast, synaptic vesicles continue to be transported to and concentrated at synapses. Milton protein is associated with mitochondria and is present primarily in axons and synapses. A likely explanation of the apparent trafficking defect is offered by the coimmunoprecipitation of Milton and kinesin heavy chain. Transfected into HEK293T cells, Milton induces a redistribution of mitochondria within the cell. We propose that Milton is a mitochondria-associated protein required for kinesin-mediated transport of mitochondria to nerve terminals.
Stowers
R Steven
RS
Department of Molecular and Cell Biology, University of California, Berkeley, Life Sciences Addition, Room #548, Berkeley, CA 94720, USA.
Megeath
Laura J
LJ
Górska-Andrzejak
Jolanta
J
Meinertzhagen
Ian A
IA
Schwarz
Thomas L
TL
D000818:Animals; D001370:Axonal Transport / Q000235:genetics*; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000302:isolation & purification*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016547:Kinesins / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification*; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000002:abnormalities* / Q000378:metabolism / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D009435:Synaptic Transmission / Q000235:genetics
D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; C470348:milt protein, Drosophila; D016547:Kinesins