Active diffusion in oocytes nonspecifically centers large objects during prophase I and meiosis I
Nucleus centering in mouse oocytes results from a gradient of actin-positive vesicle activity and is essential for developmental success. Here, we analyze 3D model simulations to demonstrate how a gradient in the persistence of actin-positive vesicles can center objects of different sizes. We test model predictions by tracking the transport of exogenous passive tracers. The gradient of activity induces a centering force, akin to an effective pressure gradient, leading to the centering of oil droplets with velocities comparable to nuclear ones. Simulations and experimental measurements show that passive particles subjected to the gradient exhibit biased diffusion toward the center. Strikingly, we observe that the centering mechanism is maintained in meiosis I despite chromosome movement in the opposite direction; thus, it can counteract a process that specifically off-centers the spindle. In conclusion, our findings reconcile how common molecular players can participate in the two opposing functions of chromosome centering versus off-centering.
Colin, A., Letort, G., Razin, N., Almonacid, M., Ahmed, W., Betz, T., … & Verlhac, M. H. (2020). Active diffusion in oocytes nonspecifically centers large objects during prophase I and meiosis I. The Journal of Cell Biology, 219(3). [link]
Active diffusion positions the nucleus in mouse oocytes
In somatic cells, the position of the cell centroid is dictated by the centrosome. The centrosome is instrumental in nucleus positioning, the two structures being physically connected. Mouse oocytes have no centrosomes, yet harbour centrally located nuclei. We demonstrate how oocytes define their geometric centre in the absence of centrosomes. Using live imaging of oocytes, knockout for the formin 2 actin nucleator, with off-centred nuclei, together with optical trapping and modelling, we discover an unprecedented mode of nucleus positioning. We document how active diffusion of actin-coated vesicles, driven by myosin Vb, generates a pressure gradient and a propulsion force sufficient to move the oocyte nucleus. It promotes fluidization of the cytoplasm, contributing to nucleus directional movement towards the centre. Our results highlight the potential of active diffusion, a prominent source of intracellular transport, able to move large organelles such as nuclei, providing in vivoevidence of its biological function.
M. Almonacid*, W. Ahmed*, M. Bussonnier, P. Mailly, T. Betz, R. Voituriez, N. Gov, M-H. Verlhac. “Active diffusion positions the nucleus in mouse oocytes”. Nature Cell Biology. 2015 (DOI:10.1038/ncb3131) [link] (* equally contributing co-first authors)
Small-scale displacement fluctuations of vesicles in fibroblasts
The intracellular environment is a dynamic space filled with various organelles moving in all directions. Included in this diverse group of organelles are vesicles, which are involved in transport of molecular cargo throughout the cell. Vesicles move in either a directed or non-directed fashion, often depending on interactions with cytoskeletal proteins such as microtubules, actin filaments, and molecular motors. How these proteins affect the local fluctuations of vesicles in the cytoplasm is not clear since they have the potential to both facilitate and impede movement. Here we show that vesicle mobility is significantly affected by myosin-II, even though it is not a cargo transport motor. We find that myosin-II activity increases the effective diffusivity of vesicles and its inhibition facilitates longer states of non-directed motion. Our study suggests that altering myosin-II activity in the cytoplasm of cells can modulate the mobility of vesicles, providing a possible mechanism for cells to dynamically tune the cytoplasmic environment in space and time.
D. Posey, P. Blaisdell-Pijuan, S. K. Knoll, T. A. Saif, and W. Ahmed*. “Small-scale displacement fluctuations of vesicles in fibroblasts.” Scientific reports 8. 2018 (DOI:10.1038/s41598-018-31656-3) [link] (* corresponding author)