Rab27a Regulates the Peripheral Distribution of Melanosomes in Melanocytes

Hume, Alistair N.; Collinson, Lucy M.; Rapak, Andrzej; Gomes, Anita Quintal; Hopkins, Colin R.; Seabra, Miguel C.

doi:10.1083/jcb.152.4.795

Cited by 307 publications

(344 citation statements)

References 59 publications

(82 reference statements)

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“…Co-immunostaining for RAB27A and MYO5A in wild type human and mouse melanocytes revealed colocalization as well as localization with black end-stage melanosome (26,27). Moreover, MYO5A and RAB27A coimmunoprecipitate in extracts from melanocytes (28). In dilute and ashen melanocytes the melanosomes undergo fast bidirectional, microtubule-dependent movement between the perinuclear region and the dendrite periphery, but peripheral melanosome capture seems not possible.…”

Section: Rab27a the Second Candidate Genementioning

confidence: 98%

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: Rab27a the Second Candidate Genementioning

confidence: 98%

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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“…The melanosome-bound small GTPase Rab27a associates in a GTPdependent manner with the adaptor protein Mlph. Mlph in turn links MyoVa to the melanosome to form a tripartite transport complex in vivo (11)(12)(13)(14)(15)(16)(17)(18). Importantly, a functional tripartite transport complex could be reconstituted from the Rab27a, Mlph, and MyoVa in vitro (19).…”

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confidence: 99%

Myosin Va’s adaptor protein melanophilin enforces track selection on the microtubule and actin networks in vitro

Oberhofer

Spieler

Rosenfeld

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Pigment organelles, or melanosomes, are transported by kinesin, dynein, and myosin motors. As such, melanosome transport is an excellent model system to study the functional relationship between the microtubule-and actin-based transport systems. In mammalian melanocytes, it is well known that the Rab27a/melanophilin/myosin Va complex mediates actin-based transport in vivo. However, pathways that regulate the overall directionality of melanosomes on the actin/microtubule networks have not yet been delineated. Here, we investigated the role of PKA-dependent phosphorylation on the activity of the actin-based Rab27a/melanophilin/myosin Va transport complex in vitro. We found that melanophilin, specifically its C-terminal actin-binding domain (ABD), is a target of PKA. Notably, in vitro phosphorylation of the ABD closely recapitulated the previously described in vivo phosphorylation pattern. Unexpectedly, we found that phosphorylation of the ABD affected neither the interaction of the complex with actin nor its movement along actin tracks. Surprisingly, the phosphorylation state of melanophilin was instead important for reversible association with microtubules in vitro. Dephosphorylated melanophilin preferred binding to microtubules even in the presence of actin, whereas phosphorylated melanophilin associated with actin. Indeed, when actin and microtubules were present simultaneously, melanophilin's phosphorylation state enforced track selection of the Rab27a/melanophilin/ myosin Va transport complex. Collectively, our results unmasked the regulatory dominance of the melanophilin adaptor protein over its associated motor and offer an unexpected mechanism by which filaments of the cytoskeletal network compete for the moving organelles to accomplish directional transport on the cytoskeleton in vivo.melanophilin | myosin Va | intracellular transport | transport regulation

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“…Rab27a is primarily expressed in the endocrine pancreas, intestines, and parotid gland and has also been studied in melanocytes, platelets, PC12 cells, and cytotoxic T-lymphocytes. Rab27b is highly expressed in the brain, spleen, parotid gland, platelets, and exocrine pancreas (4,6,21,22,37,42,45,56).…”

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confidence: 99%

Rab27b regulates exocytosis of secretory vesicles in acinar epithelial cells from the lacrimal gland

Chiang¹,

Ngo²,

Schechter

et al. 2011

American Journal of Physiology-Cell Physiology

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mechanisms largely yet uncharacterized. We investigated the role of Rab27b in the terminal release of these secretory vesicles. Confocal fluorescence microscopy analysis of primary cultured rabbit lacrimal gland acinar cells revealed that Rab27b was enriched on the membrane of large subapical vesicles that were significantly colocalized with Rab3D and Myosin 5C. Stimulation of cultured acinar cells with the secretagogue carbachol resulted in apical fusion of these secretory vesicles with the plasma membrane. Evaluation of morphological changes by transmission electron microscopy of lacrimal glands from Rab27b Ϫ/Ϫ and Rab27 ash/ash /Rab27b Ϫ/Ϫ mice, but not ashen mice deficient in Rab27a, showed changes in abundance and organization of secretory vesicles, further confirming a role for this protein in secretory vesicle exocytosis. Glands lacking Rab27b also showed increased lysosomes, damaged mitochondria, and autophagosomelike organelles. In vitro, expression of constitutively active Rab27b increased the average size but retained the subapical distribution of Rab27b-enriched secretory vesicles, whereas dominant-negative Rab27b redistributed this protein from membrane to the cytoplasm. Functional studies measuring release of a cotransduced secretory protein, syncollin-GFP, showed that constitutively active Rab27b enhanced, whereas dominant-negative Rab27b suppressed, stimulated release. Disruption of actin filaments inhibited vesicle fusion to the apical membrane but did not disrupt homotypic fusion. These data show that Rab27b participates in aspects of lacrimal gland acinar cell secretory vesicle formation and release. actin; Rab3d; exocrine secretion; syncollin; mouse models A FUNCTIONING LACRIMAL GLAND (LG) is critical for a healthy ocular surface. This exocrine gland is the primary source of tear proteins and fluid, which, released up on the gland's exposure to sympathetic or parasympathetic agonists provided by innervating nerves, contribute to the middle aqueous layer of the precorneal film. Much of the LG's secretions originate from acinar cells, which constitute over 80% of the mass of the LG (13). These LG acinar cells produce a diverse array of secretory proteins that are internally sorted into large pools of serous and mucous secretory vesicles (SV) sized ϳ1 m in diameter and stored beneath the apical plasma membrane (APM) in preparation for regulated exocytosis. SV contents include nutrients and growth factors (lacritin and EGF), antibacterial and antiviral factors (secretory IgA and lactoferrin), and an array of proteases and lysosomal hydrolases (10, 39, 47). Despite its physiological importance, however, few studies have focused on the mechanisms of secretory membrane trafficking in LG acinar cells, in part due to the fragility and heterogeneity of these LG acinar SV relative to those in other acinar secretory cells, e.g., pancreatic acini (7).The current schematic of exocytosis in the LG acinar cell suggests multiple participants. Mature LG acinar cell SV localize beneath an actin-rich network und...

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Rab27a Regulates the Peripheral Distribution of Melanosomes in Melanocytes

Cited by 307 publications

References 59 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

Myosin Va’s adaptor protein melanophilin enforces track selection on the microtubule and actin networks in vitro

Rab27b regulates exocytosis of secretory vesicles in acinar epithelial cells from the lacrimal gland

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