Abstract
Cell biologists generally consider that microtubules and actin play complementary roles in long- and short-distance transport in animal cells. On the contrary, using melanosomes of melanocytes as a model, we recently discovered that the motor protein myosin-Va works with dynamic actin tracks to drive long-range organelle dispersion in opposition to microtubules. This suggests that in animals, as in yeast and plants, myosin/actin can drive long-range transport. Here, we show that the SPIRE-type actin nucleators (predominantly SPIRE1) are Rab27a effectors that co-operate with formin-1 to generate actin tracks required for myosin-Va-dependent transport in melanocytes. Thus, in addition to melanophilin/myosin-Va, Rab27a can recruit SPIREs to melanosomes, thereby integrating motor and track assembly activity at the organelle membrane. Based on this, we suggest a model in which organelles and force generators (motors and track assemblers) are linked, forming an organelle-based, cell-wide network that allows their collective activity to rapidly disperse the population of organelles long-distance throughout the cytoplasm.
Highlights
Cell biologists generally consider that microtubules and actin play complementary roles in long- and short-distance transport in animal cells
FMN1, SPIRE1 and SPIRE2 are required for melanosome dispersion in melanocytes
(5/5 transfections), we found that knockdown of FMN1, and double knockdown of its interacting partners SPIRE1 and SPIRE2, induced melanosome clustering like that seen for Rab27a knockdown, albeit that the extent of clustering was significantly lower (Fig. 1b, c; mean pigment area (% total); NT = 86 ± 10.28%, Rab27a = 31.28 ± 8.242%, FMN1 = 45.07 ± 8.061%
Summary
Cell biologists generally consider that microtubules and actin play complementary roles in long- and short-distance transport in animal cells. Unlike plants and yeast, microtubules (MTs) and actin filaments (AFs) are thought to regulate transport in a manner akin to the infrastructure of a developed nation[1,2,3,4] This ‘highways and local roads’ model suggests that MTs are tracks for long-range transport (highways) between the cell centre and periphery, driven by kinesin and dynein motors. AFs (local roads) and myosin motors work downstream picking up cargo at the periphery, and transporting it for the ‘last μm’ to its final destination This model makes intuitive sense as MTs in many cultured animal cells form a polarised radial network of tracks spanning >10 μm from the centrally located centrosome to the periphery and appear ideally distributed for long-range transport. Subsequent studies revealed similar defects in mutant mice (and human GS types II and III patients) lacking the small GTPase
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