Premium
Rab9A is required for delivery of cargo from recycling endosomes to melanosomes
Author(s) -
Mahanty Sarmistha,
Ravichandran Keerthana,
Chitirala Praneeth,
Prabha Jyothi,
Jani Riddhi Atul,
Setty Subba Rao gangi
Publication year - 2016
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12434
Subject(s) - endosome , melanosome , microbiology and biotechnology , nanotechnology , chemistry , biology , materials science , biochemistry , intracellular , melanin
Summary Melanosomes are a type of lysosome‐related organelle that is commonly defective in Hermansky–Pudlak syndrome. Biogenesis of melanosomes is regulated by BLOC ‐1, ‐2, ‐3, or AP ‐1, ‐3 complexes, which mediate cargo transport from recycling endosomes to melanosomes. Although several Rab GTP ases have been shown to regulate these trafficking steps, the precise role of Rab9A remains unknown. Here, we found that a cohort of Rab9A associates with the melanosomes and its knockdown in melanocytes results in hypopigmented melanosomes due to mistargeting of melanosomal proteins to lysosomes. In addition, the Rab9A‐depletion phenotype resembles Rab38/32‐inactivated or BLOC ‐3‐deficient melanocytes, suggesting that Rab9A works in line with BLOC ‐3 and Rab38/32 during melanosome cargo transport. Furthermore, silencing of Rab9A, Rab38/32 or its effector VARP , or BLOC ‐3‐deficiency in melanocytes decreased the length of STX 13‐positive recycling endosomal tubules and targeted the SNARE to lysosomes. This result indicates a defect in directing recycling endosomal tubules to melanosomes. Thus, Rab9A and its co‐regulatory GTP ases control STX 13‐mediated cargo delivery to maturing melanosomes.