Iva Marija Tolic-Norrelykke

Iva Marija Tolic-Norrelykke, MPI-CBG Dresden Core expertise: self-organization of dynein motors generates meiotic nuclear oscillations Molecular motors, exerting force on microtubules, position nuclei, spindles, and other organelles in eukaryotic cells. Much is known about the behavior of individual molecular motors in vitro. However, how a multitude of motors and microtubules organise their behavior into a concerted movement in vivo remains unclear. The vigorous nuclear oscillations in meiotic prophase of the fission yeast Schizosaccharomyces pombe provide an example of a movement dependent on cytoplasmic dynein and microtubules. We propose a mechanism of these oscillations based on collective behavior of dynein motors and dynamic microtubules. By perturbing the force balance using laser ablation of microtubules, we show that the nuclear movement is driven by pulling forces exerted along the lateral links between the leading microtubules and the cell cortex. Observation of dynein dynamics revealed that when these dynein-mediated links between the microtubules and the cortex break, dynein detaches from the cortex and remains on the microtubules. Dynein distribution on the microtubules was asymmetric, with more dynein attached to the leading than to the trailing microtubules.

In order to identify the key mechanisms necessary to account for the observed nuclear movement, we developed a minimal one-dimensional model based on the above experimental results and the known physical properties of motors. Motors attach to dynamic microtubules and link them to the cortex. The attachment rate depends on microtubule length and motor concentration; the detachment rate is load-dependent. The linked motors generate a force on the microtubules described by a force-velocity relationship. This model accounts for the triangular waveform of the observed oscillations, as well as the observed positive feedback of the movement on the amount of motors on the leading microtubule. Our work provides the first direct in vivo observation of self-organised dynamic dynein distributions, which, due to the intrinsic motor properties, generate regular large-scale movements in the cell.