Identification of an organelle receptor for myosin-Va

Nat Cell Biol. 2002 Apr;4(4):271-8. doi: 10.1038/ncb760.


Little is known about how molecular motors bind to their vesicular cargo. Here we show that myosin-Va, an actin-based vesicle motor, binds to one of its cargoes, the melanosome, by interacting with a receptor-protein complex containing Rab27a and melanophilin, a postulated Rab27a effector. Rab27a binds to the melanosome first and then recruits melanophilin, which in turn recruits myosin-Va. Melanophilin creates this link by binding to Rab27a in a GTP-dependent fashion through its amino terminus, and to myosin-Va through its carboxy terminus. Moreover, this latter interaction, similar to the ability of myosin-Va to colocalize with melanosomes and influence their distribution in vivo, is absolutely dependent on the presence of exon-F, an alternatively spliced exon in the myosin-Va tail. These results provide the first molecular description of an organelle receptor for an actin-based motor, illustrate how alternate exon usage can be used to specify cargo, and further expand the functional repertoire of Rab GTPases and their effectors.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alternative Splicing
  • Animals
  • Animals, Newborn
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Exons
  • Green Fluorescent Proteins
  • Kinetics
  • Luminescent Proteins / metabolism
  • Melanocytes / metabolism
  • Melanosomes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Models, Genetic
  • Myosin Type V / chemistry*
  • Myosin Type V / metabolism*
  • Phenotype
  • Plasmids / metabolism
  • Protein Binding
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Transfection
  • Two-Hybrid System Techniques
  • rab GTP-Binding Proteins / chemistry
  • rab GTP-Binding Proteins / metabolism*
  • rab27 GTP-Binding Proteins
  • rab3A GTP-Binding Protein / metabolism


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Luminescent Proteins
  • Mlph protein, mouse
  • Protein Isoforms
  • rab27 GTP-Binding Proteins
  • Green Fluorescent Proteins
  • Myosin Type V
  • Rab27a protein, mouse
  • rab GTP-Binding Proteins
  • rab3A GTP-Binding Protein