Ciarán BUTLER-HALLISSEY                    Harrison YORK

Mapping microtubule turnover and remodelling during neuron development

Neurons have a complex cytoskeletal architecture which enables a stable polarised arborisation that lasts decades, but can also undergo dynamic rearrangements underlying development, learning and adaption. Central to this balance of stability and plasticity are microtubules, dynamic polymers of tubulin that support the long-range transport of neuronal components. In this seminar we will present two on-going projects within the Leterrier (NeuroCyto) Lab aimed towards understanding mechanistically how neurons regulate the turnover (1) and function (2) of subcellular populations of microtubules. Microtubules grow and shrink from their tips but recent studies have shown that they can also be renewed by directly incorporating tubulin into their assembled lattices, which we hypothesise may be critical for the long-lifetimes of neuronal microtubules. Firstly, we will present how using microinjection of labelled tubulin in combination with super-resolution microscopy, we are able to dissect the differential patterns of microtubule in-lattice renewal and plus-tip growth during the process of neurite specification in ex vivo cultures of embryonic rat hippocampal neurons. In the second part of the seminar, we will describe a newer project investigating how tubulin conformational changes within the shafts of microtubules may act as reversible signals, dictating the preferential binding of different microtubule associated proteins (MAPs). These MAPs can in turn, influence the binding and trafficking of motor proteins, thereby dictate the spatiotemporal distribution of organelles and other neuronal cargo. Together these projects represent on-going efforts within the team to uncover general mechanisms by which molecular-scale interactions of the microtubule cytoskeleton can support polarity emergence and neuronal cellular organisation.