Axonal transport of mitochondria to synapses depends on milton, a novel Drosophila protein

Neuron. 2002 Dec 19;36(6):1063-77. doi: 10.1016/s0896-6273(02)01094-2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axonal Transport / genetics*
  • Cells, Cultured
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / genetics
  • Drosophila Proteins / isolation & purification*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / ultrastructure
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Humans
  • Immunohistochemistry
  • Kinesin / metabolism
  • Male
  • Microscopy, Electron
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Molecular Sequence Data
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / isolation & purification*
  • Nervous System Malformations / genetics
  • Nervous System Malformations / metabolism
  • Photoreceptor Cells, Invertebrate / abnormalities*
  • Photoreceptor Cells, Invertebrate / metabolism
  • Photoreceptor Cells, Invertebrate / ultrastructure
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Protein Transport / genetics
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Synaptic Transmission / genetics

Substances

  • Drosophila Proteins
  • Nerve Tissue Proteins
  • milt protein, Drosophila
  • Kinesin

Associated data

  • GENBANK/AY038000
  • GENBANK/AY038001