title: Cyclic AMP promotes a peripheral distribution of melanosomes and stimulates melanophilin/Slac2-a and actin association.
abstract: Melanosomes are melanin-containing organelles that belong to a recently individualized group of lysosome-related organelles. Recently, numerous reports have dissected the molecular mechanisms that control melanosome transport, but nothing was known about the possible regulation of melanosome distribution by exogenous physiological stimulus. In the present report, we demonstrate that a physiological melanocyte-differentiating agent such as alpha-melanocyte-stimulating hormone, through the stimulation of the cAMP pathway, induces a rapid centrifugal transport of melanosomes, leading to their accumulation at the dendrite tips of melanocytes. Interestingly, the small GTP binding proteins of the p21Rho family and one of their effectors, p160 Rho-associated kinase, but not PKA, play a key role in redistribution of melanosomes at the extremities of the dendrites. Further, we have investigated, at the molecular level, the effect of cAMP on the different proteins involved in the control of melanosome transport. We demonstrate that cAMP stimulates the expression of Rab27a and rapidly increases the interaction of the melanophilin/Slac2-a with actin. Thus, we propose that the stimulation of the interaction between melanophilin/Slac2-a and actin would allow the rapid accumulation of melanosomes in the actin-rich region of the dendrite extremities.
authors.affiliation: INSERM U597, Biologie et Pathologie des Celllules Mélanocytaires, Faculté de Médecine, Nice, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Passeron
authors.forename: Philippe
authors.initials: P
authors.lastname: Bahadoran
authors.forename: Corine
authors.initials: C
authors.lastname: Bertolotto
authors.forename: Christine
authors.initials: C
authors.lastname: Chiaverini
authors.forename: Roser
authors.initials: R
authors.lastname: Buscà
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Valony
authors.forename: Karine
authors.initials: K
authors.lastname: Bille
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Ortonne
authors.forename: Robert
authors.initials: R
authors.lastname: Ballotti
mesh_terms: D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology; D020460:Melanosomes / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D018995:Myosin Heavy Chains / Q000378:metabolism; D024701:Myosin Type V / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000521:alpha-MSH / Q000494:pharmacology; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000075745:rab27 GTP-Binding Proteins; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C492410:MLPH protein, human; C435724:Mlph protein, mouse; C513082:Myo5a protein, mouse; D000075745:rab27 GTP-Binding Proteins; C077511:MYO5A protein, human; D005576:Colforsin; D000521:alpha-MSH; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D024701:Myosin Type V; C066694:RAB27A protein, human; C512962:Rab27a protein, mouse; D018995:Myosin Heavy Chains; D020691:rab GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein