title: Regulation of bidirectional melanosome transport by organelle bound MAP kinase.
abstract: Regulation of intracellular transport plays a role in a number of processes, including mitosis, determination of cell polarity, and neuronal growth. In Xenopus melanophores, transport of melanosomes toward the cell center is triggered by melatonin, whereas their dispersion throughout the cytoplasm is triggered by melanocyte-stimulating hormone (MSH), with both of these processes mediated by cAMP-dependent protein kinase A (PKA) activity [1, 2]. Recently, the ERK (extracellular signal-regulated kinase) pathway has been implicated in regulating organelle transport and signaling downstream of melatonin receptor [3, 4]. Here, we directly demonstrate that melanosome transport is regulated by ERK signaling. Inhibition of ERK signaling by the MEK (MAPK/ERK kinase) inhibitor U0126 blocks bidirectional melanosome transport along microtubules, and stimulation of ERK by constitutively active MEK1/2 stimulates transport. These effects are specific because perturbation of ERK signaling has no effect on the movement of lysosomes, organelles related to melanosomes [5]. Biochemical analysis demonstrates that MEK and ERK are present on melanosomes and transiently activated by melatonin. Furthermore, this activation correlates with an increase in melanosome transport. Finally, direct inhibition of PKA transiently activates ERK, demonstrating that ERK acts downstream of PKA. We propose that signaling of organelle bound ERK is a key pathway that regulates bidirectional, microtubule-based melanosome transport.
authors.affiliation: Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Sean W
authors.initials: SW
authors.lastname: Deacon
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nascimento
authors.forename: Anna S
authors.initials: AS
authors.lastname: Serpinskaya
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Gelfand
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002070:Butadienes / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D008547:Melanophores / Q000378:metabolism*; D020460:Melanosomes / Q000378:metabolism* / Q000502:physiology; D008550:Melatonin; D008870:Microtubules / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014162:Transfection; D014981:Xenopus / Q000502:physiology*
chemical_list: D002070:Butadienes; D017931:DNA Primers; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D049452:Green Fluorescent Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D008550:Melatonin