Going ‘off-road’, the molecular mechanism of vesicle originated actin/myosin transport

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In our aim to explore the function of actin/myosin force generation in vesicle transport processes, we have discovered a novel transport mechanism in mouse oocytes and melanocytes, which is based on a vesicle originated actin/myosin network. Important factors driving the transport have been identified and include vesicle associated RAB GTPases, class 5 myosin motor proteins, the SPIRE/formin actin nucleator complex and the melanophilin myosin/actin filament/microtubule binding protein. Major questions concerning the mode and order of action of the different factors and the actual force generation mechanism are not yet understood. Our model would suggest that SPIRE/formin cooperation generates actin filaments and that a vesicle interacts in parallel with two actin filaments, in an anchoring and in a processive filament sliding mode. By employing immortalised melanocytes and melanosome transport as a cell culture model system, in combination with in vitro reconstitution of actin/myosin driven motility of microspheres and mathematical modelling, we here propose to study the mechanistic principles of the vesicle originated actin/myosin transport. Our study will contribute to the cell biological understanding of exocytic vesicle transport processes, which determine the polarisation and communication of animal cells.