Rab27A-binding protein Slp2-a is required for peripheral melanosome distribution and elongated cell shape in melanocytes

Taruho S. Kuroda, Mitsunori Fukuda

Research output: Contribution to journalArticlepeer-review

125 Citations (Scopus)

Abstract

The synaptotagmin-like protein (Slp) family is implicated in regulating Rab27A-mediated membrane transport, but how it might do this is unknown. Here we report that Slp2-a, a previously uncharacterized Rab27A-binding protein in melanocytes, controls melanosome distribution in the cell periphery and regulates the morphology of melanocytes. Slp2-a is the most abundantly expressed of the Slp- and Slac2-family proteins in melanocytes and colocalizes with Rab27A on melanosomes. Knockdown of endogenous Slp2-a protein by small-interfering RNAs (siRNAs) markedly reduced the number of melanosomes in the cell periphery of mouse melanocytes ('peripheral dilution'). Expression of siRNA-resistant Slp2-a (Slp2-aSR) rescued the peripheral dilution of melanosomes induced by Slp2-a siRNAs, but Slp2-aSR mutants, which failed to interact with either phospholipids or Rab27A, did not. Loss of Slp2-a protein also induced a change in melanocyte morphology, from their normal elongated shape to a more rounded shape, which depended on the phospholipid-binding activity of Slp2-a, but not on its Rab27A-binding activity. By contrast, knockdown of Slac2-a (also called melanophilin), another Rab27A-binding protein in melanocytes, caused perinuclear aggregation of melanosomes alone without altering cell shape. These results reveal the differential and sequential roles of Rab27A-binding proteins in melanosome transport in melanocytes.

Original languageEnglish
Pages (from-to)1195-1203
Number of pages9
JournalNature cell biology
Volume6
Issue number12
DOIs
Publication statusPublished - 2004 Dec
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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