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Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes

Christina Wasmeier1, Maryse Romao, Lynn Plowright

  • 1Molecular and Cellular Medicine, Division of Biomedical Sciences, Imperial College London, London SW7 2AZ, England, UK.

The Journal of Cell Biology
|October 18, 2006
PubMed

Insights

The small GTPase Rab38 is crucial for melanogenesis, but Rab32 compensates for its loss. Loss of both Rab38 and Rab32 impairs melanosome formation by mistargeting key enzymes like tyrosinase.

Area of Science:

  • Cell Biology
  • Genetics
  • Biochemistry

Background:

  • A mutation in the small GTPase Rab38 causes the "chocolate" (cht) mouse coat color phenotype, suggesting its involvement in melanogenesis.
  • The precise function of Rab38 in pigment production remains unclear.

Purpose of the Study:

  • To elucidate the role of Rab38 in melanogenesis.
  • To investigate the functional relationship between Rab38 and Rab32 in pigment production.

Main Methods:

  • Analysis of the cht Rab38(G19V) mutation.
  • Functional compensation studies using Rab32-specific small interfering RNA.
  • Immunolocalization of Rab38, Rab32, tyrosinase, and tyrosinase-related protein 1.
  • Assessment of enzyme trafficking in Rab38/Rab32-deficient cells.

Main Results:

  • The cht Rab38(G19V) mutation results in an inactive protein.
  • Rab32 functionally compensates for the loss of Rab38 in melanocytes.
  • Depletion of Rab32 in cht cells leads to severe pigmentation loss.
  • Rab38 and Rab32 are involved in the sorting of tyrosinase and tyrosinase-related protein 1 to melanosomes.
  • In Rab38/Rab32-deficient cells, tyrosinase is mistargeted and degraded after leaving the trans-Golgi network (TGN).

Conclusions:

  • Rab38 and Rab32 play a critical role in the intracellular trafficking of melanogenic enzymes from the TGN to melanosomes.
  • This Rab38/Rab32 subfamily is essential for melanosome biogenesis and potentially other lysosome-related organelles.

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