title: Myosin-Va and dynamic actin oppose microtubules to drive long-range organelle transport.
abstract: In animal cells, microtubule and actin tracks and their associated motors (dynein, kinesin, and myosin) are thought to regulate long- and short-range transport, respectively. Consistent with this, microtubules extend from the perinuclear centrosome to the plasma membrane and allow bidirectional cargo transport over long distances (>1 μm). In contrast, actin often comprises a complex network of short randomly oriented filaments, suggesting that myosin motors move cargo short distances. These observations underpin the "highways and local roads" model for transport along microtubule and actin tracks. The "cooperative capture" model exemplifies this view and suggests that melanosome distribution in melanocyte dendrites is maintained by long-range transport on microtubules followed by actin/myosin-Va-dependent tethering. In this study, we used cell normalization technology to quantitatively examine the contribution of microtubules and actin/myosin-Va to organelle distribution in melanocytes. Surprisingly, our results indicate that microtubules are essential for centripetal, but not centrifugal, transport. Instead, we find that microtubules retard a centrifugal transport process that is dependent on myosin-Va and a population of dynamic F-actin. Functional analysis of mutant proteins indicates that myosin-Va works as a transporter dispersing melanosomes along actin tracks whose +/barbed ends are oriented toward the plasma membrane. Overall, our data highlight the role of myosin-Va and actin in transport, and not tethering, and suggest a new model in which organelle distribution is determined by the balance between microtubule-dependent centripetal and myosin-Va/actin-dependent centrifugal transport. These observations appear to be consistent with evidence coming from other systems showing that actin/myosin networks can drive long-distance organelle transport and positioning.
authors: School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK.
authors: Richard D
authors: RD
authors: Evans
authors: School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK.
authors: Christopher
authors: C
authors: Robinson
authors: School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK.
authors: Deborah A
authors: DA
authors: Briggs
authors: School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK.
authors: David J
authors: DJ
authors: Tooth
authors: CEDOC Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, 1169-056 Lisbon, Portugal.
authors: Jose S
authors: JS
authors: Ramalho
authors: Centro Nacional de Biotecnologia (CNB-CSIC), Madrid 28049, Spain; CIBERER-ISCIII, Madrid 28029, Spain.
authors: Marta
authors: M
authors: Cantero
authors: Centro Nacional de Biotecnologia (CNB-CSIC), Madrid 28049, Spain; CIBERER-ISCIII, Madrid 28029, Spain.
authors: Lluis
authors: L
authors: Montoliu
authors: Cell Signalling Research Centre, Division of Biomedical Sciences, St. George's, University of London, London SW17 0RE, UK.
authors: Shyamal
authors: S
authors: Patel
authors: Cell Signalling Research Centre, Division of Biomedical Sciences, St. George's, University of London, London SW17 0RE, UK.
authors: Elena V
authors: EV
authors: Sviderskaya
authors: School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK. Electronic address: alistair.hume@nottingham.ac.uk.
authors: Alistair N
authors: AN
authors: Hume
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D020460:Melanosomes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000378:metabolism*; D024701:Myosin Type V / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D015388:Organelles / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D053778:Thiazolidines / Q000494:pharmacology; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011500:Protein Synthesis Inhibitors; D053778:Thiazolidines; D050257:Tubulin Modulators; D024701:Myosin Type V; D015739:Nocodazole; C037067:latrunculin A