Cyclic AMP promotes a peripheral distribution of melanosomes and stimulates melanophilin/Slac2‐a and actin association

Passeron, Thierry; Bahadoran, Philippe; Bertolotto, Corine; Chiavérini, C.; Buscà, Roser; Valony, Gaëlle; Bille, Karine; Ortonne, Jean‐Paul; Ballotti, Robert

doi:10.1096/fj.03-1240fje

Cited by 50 publications

(35 citation statements)

References 55 publications

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“…This physiological phenomenon is induced by UV exposure and helps protect the skin from the carcinogenic action of UV irradiation. The activation of melanocortin I receptor receptors at the surface of melanocytes by ␣-MSH secreted by surrounding keratinocytes leads to the activation of the cAMP pathway, which plays a key role not only in the process of melanogenesis but also in the transport of melanosomes (20,26). The downstream activation of CRE, then MITF, and finally the DCT and tyrosinase promoters is considered the main pathway leading to the production of melanin (27,28).…”

Section: Discussionmentioning

confidence: 99%

SOX9 is a key player in ultraviolet B-induced melanocyte differentiation and pigmentation

Passeron

Valencia

Bertolotto

et al. 2007

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

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121

115

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SOX (SRY type HMG box) proteins are transcription factors that are predominantly known for their roles during development. During melanocyte development from the neural crest, SOX10 regulates microphthalmia-associated transcription factor, which controls a set of genes critical for pigment cell development and pigmentation, including dopachrome tautomerase and tyrosinase. We report here that another SOX factor, SOX9, is expressed by melanocytes in neonatal and adult human skin and is up-regulated by UVB exposure. We demonstrate that this regulation is mediated by cAMP and protein kinase. We also show that agouti signal protein, a secreted factor known to decrease pigmentation, down-regulates SOX9 expression. In adult and neonatal melanocytes, SOX9 regulates microphthalmia-associated transcription factor, dopachrome tautomerase, and tyrosinase promoters, leading to an increase in the expression of these key melanogenic proteins and finally to a stimulation of pigmentation. SOX9 completes the complex and tightly regulated process leading to the production of melanin by acting at a very upstream level. This role of SOX9 in pigmentation emphasizes the poorly understood impact of SOX proteins in adult tissues.microphthalmia-associated transcription factor ͉ tyrosinase ͉ protein kinase A ͉ melanocyte-stimulating hormone ͉ agouti signal protein S ox (SRY type HMG box) proteins are transcription factors that belong to the HMG box superfamily of DNA-binding proteins and play a key role during development. SOX9 belongs to the SOX-E subgroup, which includes SOX8, SOX9, and SOX10. The structures of these proteins show a high conservation and similar positions of their HMG boxes (1). SOX10 has been shown to play a key role in the regulation of melanocyte differentiation (2), and mutations in SOX10 lead to Waardenburg syndrome type 4, a genetic hypomelanosis with deafness and megacolon (3). During melanocyte development from the neural crest, SOX10 regulates the expression of microphthalmia-associated transcription factor (MITF), which in turn controls a set of genes critical for pigment cell development and pigmentation (4). Indeed, in conjunction with other transcription factors, MITF regulates dopachrome tautomerase (DCT), tyrosinase (the limiting enzyme for melanogenesis), and tyrosinase-related protein 1 (TYRP1). All of these proteins are essential for the full differentiation of melanocytes and are directly involved in melanin synthesis. SOX10 also acts as a critical transactivator of DCT, which MITF, on its own, is insufficient to stimulate (5-7).SOX9 has a key role in sexual determination and chondrogenesis, and mutations in SOX9 can lead to campomelic dysplasia, a skeletal dysmorphology associated in most XY cases with sex reversal (8, 9). During embryonic development, the SOX9 gene becomes active in all prechondrocytic mesenchymal condensations, and its expression is maintained at high levels in fully differentiated chondrocytes. The direct target for SOX9 is a chondrocyte-specific enhancer in the gene for collagen ...

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Section: Discussionmentioning

confidence: 99%

SOX9 is a key player in ultraviolet B-induced melanocyte differentiation and pigmentation

Passeron

Valencia

Bertolotto

et al. 2007

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

Self Cite

121

115

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“…The myosin V class, comprising myosin Va, Vb, and Vc, was recently shown to be required for the endocytic recycling of a series of receptors (17,18,(21)(22)(23)(24)(25)(26)(27)30). To test whether the class V myosins are involved in the vesicular transport of NPC1L1, we co-expressed the EGFP-tagged CT domains of myosins Va, Vb, and Vc with RFP-tagged NPC1L1.…”

Section: Mf Is Required For the Cholesterol-regulated Endocyticmentioning

confidence: 99%

“…Myosin Va is expressed mainly in neuronal tissues (19,20), whereas myosins Vb and Vc are universally expressed with enrichment in epithelial cells (21,22). Class V myosins are recruited to their targeting vesicles by small GTPase proteins (Rab) (23). Rab11a and Rab11 family-interacting protein 2 (Rab11-FIP2) facilitate the binding of myosin Vb to the cargo proteins of endocytic recycling vesicles (24 -28).…”

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confidence: 99%

Requirement of Myosin Vb·Rab11a·Rab11-FIP2 Complex in Cholesterol-regulated Translocation of NPC1L1 to the Cell Surface

Chu¹,

Ge²,

Xie

et al. 2009

Journal of Biological Chemistry

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Niemann-Pick C1-like 1 (NPC1L1) plays a critical role in the enterohepatic absorption of free cholesterol. Cellular cholesterol depletion induces the transport of NPC1L1 from the endocytic recycling compartment to the plasma membrane (PM), and cholesterol replenishment causes the internalization of NPC1L1 together with cholesterol via clathrin-mediated endocytosis. Although NPC1L1 has been characterized, the other proteins involved in cholesterol absorption and the endocytic recycling of NPC1L1 are largely unknown. Most of the vesicular trafficking events are dependent on the cytoskeleton and motor proteins. Here, we investigated the roles of the microfilament and microfilament-associated triple complex composed of myosin Vb, Rab11a, and Rab11-FIP2 in the transport of NPC1L1 from the endocytic recycling compartment to the PM. Interfering with the dynamics of the microfilament by pharmacological treatment delayed the transport of NPC1L1 to the cell surface. Meanwhile, inactivation of any component of the myosin Vb⅐Rab11a⅐Rab11-FIP2 triple complex inhibited the export of NPC1L1. Expression of the dominant-negative mutants of myosin Vb, Rab11a, or Rab11-FIP2 decreased the cellular cholesterol uptake by blocking the transport of NPC1L1 to the PM. These results suggest that the efficient transport of NPC1L1 to the PM is dependent on the microfilament-associated myosin Vb⅐Rab11a⅐Rab11-FIP2 triple complex.

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“…B16 cells also displayed severely decreased melanosome secretion when cultured in the presence of cytochalasin-D, suggesting that the depression of melanosome release is also the consequence of the alternation in the actin polymerization/depolymerization balance induced by syntaxin3, provided that the final process of melanosome delivery is strictly controlled by actin fibers at the cell periphery (Kuroda and Fukuda, 2005;Passeron et al, 2004). The change in cell shape has been thought to be deeply involved in melanosome secretion (Jungbauer et al, 2004), but there is scant data on the regulators of actin dynamics in melanocytes.…”

Section: Discussionmentioning

confidence: 99%

“…The nascent melanosomes, which are associated with a GTP-bound form of Rab27A, are bound by the synaptotagmin-like effectors Slac2a and Slp2a and delivered to the cell periphery along microtubules and F-actin (Fukuda and Kuroda, 2002;Kuroda and Fukuda, 2005). At the peripheral dendritic filopodia, the locomotion of the melanosome-Slac2a complexes is strictly controlled by actin fibers (Kuroda and Fukuda, 2005;Passeron et al, 2004). Slp2a has C2 domains that enable an interaction with phosphatidylserine and phosphatidylinositol 4,5-bisphosphate as well as certain t-SNARE syntaxins at the plasma membrane (Gaffaney et al, 2008;Stein et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Ectopic Expression of Syntaxin3 Affects Behaviors of B16 Melanoma by Controlling Actin Dynamics

Shono

Yoshioka

Chatani

et al. 2013

Cell Struct. Funct.

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ABSTRACT. The melanin granules are synthesized in melanocytes in the epidermal basal layer and the hair matrix. For the effective passage of melanin granules to the adjacent keratinocytes, melanocytes utilize unique cytoplasmic delivery system in which cytoskeletal network is prominently involved. Here, we show that the t-SNARE protein syntaxin3, a member of a family of key mediators of the cytoplasmic vesicle fusion and potent modulators of cytoskeletal dynamics, dramatically affects melanocyte cell behavior. Although plasmalemmal syntaxin3 has been detected also on the melanosomes of normal human melanocytes, we noticed that mouse melanoma B16 cells had completely lost endogenous syntaxin3. In response to the forcible expression of syntaxin3, B16 cells formed well-developed dendritic filopodia and accumulated melanin granules in the cytoplasm. We found that exogenous syntaxin3 was not expressed at the plasma membrane, but rather, localized with non-fibrous F-actin and melanin-packed melanosomes in the cytoplasm, by which the assembly/ polymerization of actin was dramatically impacted and the melanosome secretion was severely suppressed. The syntaxin3-triggered phenotypic changes were also induced by a syntaxin3 mutant lacking SNARE and transmembrane domains, and they were completely reverted by the subsequent knockdown of exogenous syntaxin3. This t-SNARE protein may act as a regulator of the actin dynamics, rather than a direct vesicle fusion mediator, to determine the fundamental properties of melanocytes.

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Cyclic AMP promotes a peripheral distribution of melanosomes and stimulates melanophilin/Slac2‐a and actin association

Cited by 50 publications

References 55 publications

SOX9 is a key player in ultraviolet B-induced melanocyte differentiation and pigmentation

SOX9 is a key player in ultraviolet B-induced melanocyte differentiation and pigmentation

Requirement of Myosin Vb·Rab11a·Rab11-FIP2 Complex in Cholesterol-regulated Translocation of NPC1L1 to the Cell Surface

Ectopic Expression of Syntaxin3 Affects Behaviors of B16 Melanoma by Controlling Actin Dynamics

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