Rab27a and MyoVa are the primary Mlph interactors regulating melanosome transport in melanocytes

Alistair N. Hume*, Dmitry S. Ushakov, Abul K. Tarafder, Michael A. Ferenczi, Miguel C. Seabra

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)


Melanosome transport in melanocytes is a model system for the study of cytoskeletal regulation of intracellular transport. Melanophilin (Mlph) is a Rah27a- and myosin Va (MyoVa)-binding protein that regulates this process. Using yeast two-hybrid screening, we identified MT plus-end binding protein (EB1) as a melanocyte-expressed Mlph-interacting protein. To address the role of EB1 versus Rab27a and MyoVa interactions in Mlph targeting and function, we used siRNA and Mlph mutations to specifically disrupt each interaction in cultured melanocytes. Using the Mlph R35W mutant that blocks Mlph-Rab27a interaction and Rab27a siRNA we show this interaction is required for melanosome targeting and stability of Mlph. Mutants and siRNA that affect Mlph-MyoVa and Mlph-EB1 interactions reveal that while neither MyoVa nor EB1 affect Mlph targeting to melanosomes, MyoVa but not EB1 interaction is required for transport of melanosomes to peripheral dendrites. We propose that Mlph is targeted to and/or stabilised on melanosomes by Rab27a, and then recruits MyoVa, which provides additional stability to the complex and allows melanosomes to transfer from MT to actin-based transport and achieve peripheral distribution. EB1 appears to be non-essential to this process in cultured melanocytes, which suggests that it plays a redundant role and/or is required for melanocyte/keratinocyte contacts and melanosome transfer.

Original languageEnglish
Pages (from-to)3111-3122
Number of pages12
JournalJournal of Cell Science
Issue number17
Publication statusPublished - 1 Sept 2007


  • EB1
  • Melanophilin
  • Melanosome
  • Myosin Va
  • Rab27a


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