Feedback mechanisms link tubulin PTMs to Golgi organization

Project Summary/Abstract Regulation of the microtubule cytoskeleton is essential for critical cellular processes at all stages of life. Microtubules are dynamic filaments generated by polymerization of the protein tubulin, one of the most conserved proteins across the eukaryotic kingdom. Microtubule functions are determined by the Tubulin Code which posits that, in cells, specific microtubules are distinguished biochemically by post-translational modifications (PTMs) of tubulin that determine specific functional outputs. An important PTM for microtubule function during intracellular trafficking and cell migration is detyrosination in which the C-terminal tyrosine of a- tubulin is enzymatically removed. The mechanisms by which specific subsets of microtubules are selected for modification is a major knowledge gap in the field. The overarching goal of this proposal is to define the mechanisms by which individual microtubules are identified and chosen in cells for specific microtubule post- translational modifications. I will utilize biochemical and cell biology-based approaches to determine how cells utilize mechanical cues to drive microtubule PTMs and how these cues may be altered to drive aberrant cell processes including enhanced polarized secretion and cell migration. Combined, this work will greatly advance the dynamic and emerging knowledge in the field of how cells utilize writers and readers of the Tubulin Code to modify microtubule tracks and promote cell migration in normal and disease contexts.