Small GTPase Rab3A is Associated with Melanosomes in Melanoma Cells

Araki, Kento; Horikawa, Tsuyoshi; Chakraborty, Ashok; Nakagawa, Kōichi; Itoh, Hiroshi; Oka, Masahiro; Funasaka, Yoko; Pawelek, John M.; Ichihashi, Masamitsu

doi:10.1034/j.1600-0749.2000.130505.x

Cited by 32 publications

(24 citation statements)

References 12 publications

(15 reference statements)

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“…Rab3A, known to be involved in exocytosis of synaptic vesicles, was shown to be present in enriched melanosomal fractions in murine immortalized melanocytes and melanoma cells (33,34). Independently, two groups showed by confocal microscopy and immuno-electron microscopy that it colocalizes with the melanosome membrane, particularly in the perinuclear area, but not on melanosomes in the periphery of the dendrites.…”

Section: What About Leaden?mentioning

confidence: 95%

The Dilute Locus and Griscelli Syndrome: Gateways Towards a Better Understanding of Melanosome Transport

Westbroek

Lambert

Naeyaert

2001

Pigment Cell Research

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would present a major breakthrough in the possibilities to In this review an overview of recent advances in the understanding of melanosome movement within epidermal influence pigmentation and related disorders, of great concern melanocytes is given. Exploration of the molecular events to some patients. Moreover, melanosome transport offers a good model to study mammalian organelle trafficking and its involved in and determining the process of melanosome transkey players in general. port, as an essential part of human pigmentation, could lead to the identification of agents that augment, or down-regulate the Key words: Actin, Melanocyte, Motor proteins, Tubulin transfer of melanosomes to surrounding keratinocytes. This in melanosome transport has stagnated somewhat, and the focus was aimed at new molecular families involved in vesicle trafficking. Starting from an overview of the knowledge obtained with relation to molecular motors, the newly discovered involvement and co-operation of other molecules will be summarized in this review. Finally, this collection of findings is depicted graphically in Fig. 1.

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Section: What About Leaden?mentioning

confidence: 95%

The Dilute Locus and Griscelli Syndrome: Gateways Towards a Better Understanding of Melanosome Transport

Westbroek

Lambert

Naeyaert

2001

Pigment Cell Research

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“…Rab3 was shown to be associated with melanosomes by subcellular fractionation, immunofluorescence, and immunoelectron microscopy (Scott & Zhao 2001, Araki et al 2000. In addition to Rab3, Rab7 and Rab8 were also found in the melanosome fraction of mouse melanoma cells by immunoblotting (Gomez et al 2001).…”

Section: Receptors and Adaptorsmentioning

confidence: 97%

Pigment Cells: A Model for the Study of Organelle Transport

Nascimento

Roland

Gelfand

2003

Annu. Rev. Cell Dev. Biol.

141

140

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Eukaryotic organisms rely on intracellular transport to position organelles and other components within their cells. Pigment cells provide an excellent model to study organelle transport as they specialize in the translocation of pigment granules in response to defined chemical signals. Pigment cells of lower vertebrates have traditionally been used as a model for these studies because these cells transport pigment organelles in a highly coordinated fashion, are easily cultured and transfected, are ideal for microsurgery, and are good for biochemical experiments, including in vitro analysis of organelle motility. Many important properties of organelle transport, for example, the requirement of two cytoskeletal filaments (actin and microtubules), the motor proteins involved, and the mechanisms of their regulation and interactions, have been studied using pigment cells of lower vertebrates. Genetic studies of mouse melanocytes allowed the discovery of essential elements involved in organelle transport including the myosin-Va motor and its receptor and adaptor molecules on the organelle surface. Future studies of pigment cells will contribute to our understanding of issues such as the cooperation among multiple motor proteins and the mechanisms of regulation of microtubule motors.

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“…In many cell types, Rab3 and Rab27 proteins exhibit extensive overlap in their subcellular distributions, localizing to dense-core secretory granules in neuroendocrine cells (17) and melanosomes in melanocytes (32). Moreover, they are able to interact with a subset of common effectors, including rabphilin-3, granuphilin/Slp4, and Noc2 (33).…”

Section: Discussionmentioning

confidence: 99%

Rab3GEP Is the Non-redundant Guanine Nucleotide Exchange Factor for Rab27a in Melanocytes

Figueiredo

Wasmeier

Tarafder

et al. 2008

Journal of Biological Chemistry

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Rab GTPases regulate discrete steps in vesicular transport pathways. Rabs require activation by specific guanine nucleotide exchange factors (GEFs) that stimulate the exchange of GDP for GTP. Rab27a controls motility and regulated exocytosis of secretory granules and related organelles. In melanocytes, Rab27a regulates peripheral transport of mature melanosomes by recruiting melanophilin and myosin Va. Here, we studied the activation of Rab27a in melanocytes. We identify Rab3GEP, previously isolated as a GEF for Rab3a, as the non-redundant Rab27a GEF. Similar to Rab27a-deficient ashen melanocytes, Rab3GEP-depleted cells show both clustering of melanosomes in the perinuclear area and loss of the Rab27a effector Mlph. Consistent with a role as an activator, levels of Rab27a-GTP are decreased in cells lacking Rab3GEP. Recombinant Rab3GEP exhibits guanine nucleotide exchange activity against Rab27a and Rab27b in vitro, in addition to its previously documented activity against Rab3. Our results indicate promiscuity in Rab GEF action and suggest that members of related but functionally distinct Rab subfamilies can be controlled by common activators.

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Small GTPase Rab3A is Associated with Melanosomes in Melanoma Cells

Cited by 32 publications

References 12 publications

The Dilute Locus and Griscelli Syndrome: Gateways Towards a Better Understanding of Melanosome Transport

The Dilute Locus and Griscelli Syndrome: Gateways Towards a Better Understanding of Melanosome Transport

Pigment Cells: A Model for the Study of Organelle Transport

Rab3GEP Is the Non-redundant Guanine Nucleotide Exchange Factor for Rab27a in Melanocytes

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