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

Mahanty, Sarmistha; Ravichandran, Keerthana; Chitirala, Praneeth; Prabha, Jyothi; Jani, Riddhi Atul; Setty, Subba Rao Gangi

doi:10.1111/pcmr.12434

Cited by 33 publications

(32 citation statements)

References 52 publications

(141 reference statements)

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“…10). Consistent with our results, very recently, during the course of revising this paper, Mahanty et al (36) have reported the involvement of Rab9A in melanogenic enzyme trafficking. Moreover, we demonstrated that RUTBC1 is able to disrupt the interaction between Rab9A and HPS4, a component of BLOC-3, a Rab32/38 GEF (12) (Fig.…”

Section: Discussionsupporting

confidence: 80%

RUTBC1 Functions as a GTPase-activating Protein for Rab32/38 and Regulates Melanogenic Enzyme Trafficking in Melanocytes

Marubashi

Shimada

Fukuda

et al. 2016

Journal of Biological Chemistry

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Two cell type-specific Rab proteins, Rab32 and Rab38 (Rab32/38), have been proposed as regulating the trafficking of melanogenic enzymes, including tyrosinase and tyrosinase-related protein 1 (Tyrp1), to melanosomes in melanocytes. Like other GTPases, Rab32/38 function as switch molecules that cycle between a GDP-bound inactive form and a GTP-bound active form; the cycle is thought to be regulated by an activating enzyme, guanine nucleotide exchange factor (GEF), and an inactivating enzyme, GTPase-activating protein (GAP), which stimulates the GTPase activity of Rab32/38. Although BLOC-3 has already been identified as a Rab32/38-specific GEF that regulates the trafficking of tyrosinase and Tyrp1, no physiological GAP for Rab32/38 in melanocytes has ever been identified, and it has remained unclear whether Rab32/38 is involved in the trafficking of dopachrome tautomerase, another melanogenic enzyme, in mouse melanocytes. In this study we investigated RUTBC1, which was originally characterized as a Rab9-binding protein and GAP for Rab32 and Rab33B in vitro, and the results demonstrated that RUTBC1 functions as a physiological GAP for Rab32/38 in the trafficking of all three melanogenic enzymes in mouse melanocytes. The results of this study also demonstrated the involvement of Rab9A in the regulation of the RUTBC1 localization and in the trafficking of all three melanogenic enzymes. We discovered that either excess activation or inactivation of Rab32/38 achieved by manipulating RUTBC1 inhibits the trafficking of all three melanogenic enzymes. These results collectively indicate that proper spatiotemporal regulation of Rab32/38 is essential for the trafficking of all three melanogenic enzymes in mouse melanocytes.

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Section: Discussionsupporting

confidence: 80%

RUTBC1 Functions as a GTPase-activating Protein for Rab32/38 and Regulates Melanogenic Enzyme Trafficking in Melanocytes

Marubashi

Shimada

Fukuda

et al. 2016

Journal of Biological Chemistry

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“…Interestingly, a recent report has demonstrated that the Rab9-RUTBC1 complex is required for the trafficking of melanogenic enzymes in melanocytes (Marubashi et al, 2016). In line with this, Rab9 has been shown to be involved together with the biogenesis of lysosome-related organelles complex 3 (BLOC-3), another Rab9 effector, in syntaxin-13-mediated cargo transport from early endosomes to maturing melanosomes (Mahanty et al, 2016). Therefore, a new role of Rab9 as a mediator of the transport towards lysosomes or lysosome-related organelles, such as melanosomes, is now beginning to emerge.…”

Section: Rab9mentioning

confidence: 71%

Bidirectional traffic between the Golgi and the endosomes – machineries and regulation

Progida

Bakke

2016

Journal of Cell Science

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The bidirectional transport between the Golgi complex and the endocytic pathway has to be finely regulated in order to ensure the proper delivery of newly synthetized lysosomal enzymes and the return of sorting receptors from degradative compartments. The high complexity of these routes has led to experimental difficulties in properly dissecting and separating the different pathways. As a consequence, several models have been proposed during the past decades. However, recent advances in our understanding of endosomal dynamics have helped to unify these different views. We provide here an overview of the current insights into the transport routes between Golgi and endosomes in mammalian cells. The focus of the Commentary is on the key molecules involved in the trafficking pathways between these intracellular compartments, such as Rab proteins and sorting receptors, and their regulation. A proper understanding of the bidirectional traffic between the Golgi complex and the endolysosomal system is of uttermost importance, as several studies have demonstrated that mutations in the factors involved in these transport pathways result in various pathologies, in particular lysosome-associated diseases and diverse neurological disorders, such as Alzheimer's and Parkinson's disease.

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“…In a recent study, we have shown that Rab9A functions in targeting REs towards melanosomes . Thus, we evaluated the regulatory role of Rab9A along with Rab7A, 11A and 22A on RE dynamics in HeLa cells.…”

Section: Resultsmentioning

confidence: 98%

Rab22A recruits BLOC ‐1 and BLOC ‐2 to promote the biogenesis of recycling endosomes

et al. 2018

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Recycling endosomes (REs) are transient endosomal tubular intermediates of early/sorting endosomes (E/SEs) that function in cargo recycling to the cell surface and deliver the cell type‐specific cargo to lysosome‐related organelles such as melanosomes in melanocytes. However, the mechanism of RE biogenesis is largely unknown. In this study, by using an endosomal Rab‐specific RNAi screen, we identified Rab22A as a critical player during RE biogenesis. Rab22A‐knockdown results in reduced RE dynamics and concurrent cargo accumulation in the E/SEs or lysosomes. Rab22A forms a complex with BLOC‐1, BLOC‐2 and the kinesin‐3 family motor KIF13A on endosomes. Consistently, the RE‐dependent transport defects observed in Rab22A‐depleted cells phenocopy those in BLOC‐1‐/BLOC‐2‐deficient cells. Further, Rab22A depletion reduced the membrane association of BLOC‐1/BLOC‐2. Taken together, these findings suggest that Rab22A promotes the assembly of a BLOC‐1‐BLOC‐2‐KIF13A complex on E/SEs to generate REs that maintain cellular and organelle homeostasis.

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

Cited by 33 publications

References 52 publications

RUTBC1 Functions as a GTPase-activating Protein for Rab32/38 and Regulates Melanogenic Enzyme Trafficking in Melanocytes

RUTBC1 Functions as a GTPase-activating Protein for Rab32/38 and Regulates Melanogenic Enzyme Trafficking in Melanocytes

Bidirectional traffic between the Golgi and the endosomes – machineries and regulation

Rab22A recruits BLOC ‐1 and BLOC ‐2 to promote the biogenesis of recycling endosomes

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