Rab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins

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 longrange transport. Here, we show that the SPIRE-type actin nucleators (predominantly SPIRE1) are Rab27a effectors that cooperate 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.

Melanin Transfer in the Epidermis: The Pursuit of Skin Pigmentation Control Mechanisms

“…Melanosome distribution within melanocytes is postulated to result from a competition between microtubule- and actin-dependent transport [ 28 ]. A recent report suggests that inter-melanosome repulsion based on actin filament dynamics could maintain the spreading of melanosomes throughout the cytoplasm, without the need for microtubule-dependent transport [ 29 ]. Furthermore, another study showed that in retinal pigment epithelium (RPE) cells, microtubule transport is essential for fast long-range transport of melanosomes and that cytoplasmic dynein is indispensable for the passage of these organelles to an actin filament-dependent transport [ 30 ].…”

Museomics Dissects the Genetic Basis for Adaptive Seasonal Coloration in the Least Weasel

“…The melanocortin-1 receptor ( MC1R ) is a well-known pigmentation gene ( García-Borrón et al 2005 ), involved in numerous cases of color polymorphism in wild and domesticated organisms ( Hubbard et al 2010 ). The spire-type actin nucleation factor 2 ( SPIRE2 ) gene has been shown to be involved in the regulation of myosin-Va-dependent melanosome dispersion in melanocytes ( Alzahofi et al 2020 ), which could indicate an indirect function in pigment distribution. None of the other genes has a known function in coloration.…”

Melanin Distribution in Human Skin: Influence of Cytoskeletal, Polarity, and Centrosome-Related Machinery of Stratum basale Keratinocytes

“…We know much about how melanin moves within MCs [ 9 , 10 , 12 , 13 , 15 , 18 , 20 , 23 , 24 ] and also about the multiple ways melanin leaves the MC to enter the KC [ 39 , 53 , 54 , 55 ]. We have started to explore how melanin remains in large part tethered to the S. basale [ 4 ], as can be seen so strikingly with routine melanin-staining protocols [ 41 ].…”

“…This model has evolved in complexity into the “cooperative capture” model [ 10 , 12 ]. Recently, a “centrifugal and centripetal” model has been proposed, which envisions a role for actin also in long distance movements [ 13 , 14 , 15 ]. Nevertheless, all models agree on a role for both MTs and actin, together with their respective motor proteins, in melanosome movement within the epidermal MC.…”