Exploring cellular complexity through cytoskeleton regulation

Speaker Professor Carolyn Moores, Institute of Structural and Molecular Biology and School of Natural Sciences, Birkbeck College

Title Exploring cellular complexity through cytoskeleton regulation

Host Joe Atherton

 

Abstract The overall goal of our research is the elucidation of essential cytoskeleton regulatory mechanisms, applying reconstitution approaches and using biochemistry, biophysics and cryo-electron microscopy. I will focus my talk on doublecortin (DCX), an essential neuronal microtubule-associated protein that localises to the growth cone of migrating neurons and which, when mutated, causes neurodevelopmental lissencephaly. DCX is built from two flexibly connected DC domains, NDC and CDC, that mediate DCX’s microtubule nucleation and stabilization activities. In vitro, NDC and CDC activities are coordinated such that while NDC stabilises the microtubule lattice, CDC facilitates its role in microtubule nucleation and selective stabilisation of 13-protofilament microtubules. Using cryo-electron tomography, we also investigated cytoskeleton organisation within mouse hippocampal neuron growth cones. Although the growth cone ultrastructure in mouse DCX knockout neurons shows no major anomalies compared to wild-type neurons, our data suggest that microtubules sustain more structural defects in the absence of DCX, highlighting the importance of microtubule integrity during growth cone migration. I will also share recent data about the mechanism of actin nucleation and stabilisation by the cytoskeleton regulator cortactin, and consider mechanistic insights from comparison of the two cytoskeleton filament systems.