Expanding the range of cytoplasmic dynein cargoes with KASH5 and Rac1

Cytoplasmic dynein is well known as a microtubule motor that drives vesicle movement and plays key roles in spindle assembly and positioning. Here, I will talk about dynein’s role in two less familiar scenarios. The first is the movement of chromosomes in prophase I of meiosis, where dynein is recruited to the outer nuclear envelope by interacting with the LINC complex protein KASH5, which connects to a SUN protein in the inner nuclear envelope and from there to meiotic telomeres. We have characterised the interaction between dynein light intermediate chains (LICs) and KASH5. Dynein movement in the cytoplasm can therefore exert force on chromosomes within the still intact nucleus, leading to telomere clustering to give the meiotic ‘bouquet’ that is vital for chromosome synaptogenesis and chiasmata formation. I will also present unpublished work that identifies an unexpected role for dynein in down-regulating Rac1 activity during cell spreading and motility downstream of LIC1 phosphorylation by JNK.