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Myosins and the dynamics of intracellular membranes

Final Report Summary - MYODYN (Myosins and the dynamics of intracellular membranes)

The general aim of the project was to understand the functions in membrane traffic of several myosins, molecular motors associated with the actin cytoskeleton, and how myosin functions are coordinated with those of two other key players in membrane traffic, the small GTPases of the RAB family and the microtubule-based motors of the kinesin family. We focused on membrane trafficking events occurring at the level of the Golgi complex. To perform it within a team gathering physicists, biochemists and cell biologists, we have developed several original methodological approaches, including minimal in vitro assays, micropatterning and live cell imaging.
The main outcomes are i) the description of the unique biochemical properties of myosin 1b explaining its essential role in the control of the architecture and dynamics of actin networks; ii) the role of myosin 1c in stabilizing actin filaments to facilitate the interactions between transport vesicles and Golgi membranes; iii) the characterization of the molecular machinery involving myosin II and the kinesin KIF20A, which allows the fission of transport vesicles from Golgi membranes. We have also identified the core machinery composed of the Golgi-associated RAB6 GTPase and microtubules that allows the targeting of transport vesicles originating from Golgi membranes toward exocytic sites located near focal adhesions.
Our work has highlighted the diversity of functions performed by myosins and allowed a better understanding of how the functions of myosins, kinesins, RAB GTPases, and the actin and microtubule cytoskeleton are coordinated to sustain membrane traffic in eukaryotic cells.