The multiple roles of the nucleo-cytoskeleton interface in muscles

Speaker: Bruno Cadot, Institut de Myologie, Paris

Muscle cells have the particularity of containing numerous nuclei that are precisely localized underneath the plasma membrane. We have  identified several mechanisms leading to this localization and they all rely on the interaction bet ween the cytoskeleton and the nuclear envelope. In particular, we have identified Nesprin-1 as the  main actor in recruiting the microtubule nucleation machinery at the nuclear envelope in muscle cel ls. Our recent results have shown that alleviating microtubules-associated forces applied to the nuc leus, by impairing Nesprin-1 localization, can be beneficial in a context of Lamin deficiency. We have also found that Lamin mutation induce a decrease in microtubule acetylation, resulting in shorter filaments and nuclear deformation. By applying a specific drug directed to microtubules plus-ends, we can restore proper muscle function. We are now investigating how compression can impact LINC complex protein distribution and thus adapt to mechanical load, to mimic in vivo situations. The lamin shell being a key element, we are performing expansion microscopy of both differentiated cells and isolated nuclei to determine the organization of lamin filaments in different contexts. Finally, we have identified a link between nuclear envelope composition and muscle cells collective behavior, a decisive aspect for muscle formation.