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Rab9A is required for delivery of cargo from recycling endosomes to melanosomes

Mahanty, Sarmistha and Ravichandran, Keerthana and Chitirala, Praneeth and Prabha, Jyothi and Jani, Riddhi Atul and Setty, Subba Rao Gangi (2016) Rab9A is required for delivery of cargo from recycling endosomes to melanosomes. In: PIGMENT CELL & MELANOMA RESEARCH, 29 (1). pp. 43-59.

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Official URL: http://dx.doi.org/10.1111/pcmr.12434


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 GTPases 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 STX13-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 GTPases control STX13-mediated cargo delivery to maturing melanosomes.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Keywords: Rab9A; Rab38; Rab32; BLOC-1; BLOC-2; BLOC-3; AP-3; HPS
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 22 Jan 2016 05:31
Last Modified: 22 Jan 2016 05:31
URI: http://eprints.iisc.ac.in/id/eprint/53140

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