The nervous system is composed of a diverse collection of polarized cells that rely on the microtubule cytoskeleton for their specialized functions. The structural and functional diversity of these cell types is reflected at the molecular level in the diversity of the microtubule building blocks, the tubulin dimers. Microtubules are composed of multiple tubulin isotypes that are modified with abundant and chemically diverse posttranslational modifications. Although microtubules were long thought of as inert transport tracks, recent discoveries from our lab and others, reveal that they are information-rich and that their isoform diversity and plethora of posttranslational modifications regulate traffic, microtubule dynamics and mechanics. This “tubulin code” supports the diverse morphology and dynamics of microtubule arrays across cell types, cell cycle and developmental stages. Perturbations in the tubulin code are a hallmark of neurodegeneration and cancers and tubulin modification enzymes are essential for normal development. Despite knowledge of the genetic and chemical complexity of tubulin and its importance to cell physiology dating back to the 1970s, our understanding of its role in microtubule functions is still in its infancy, due in large part to a lack of tools to study the tubulin code. The Roll-Mecak laboratory has pioneered biochemical and biophysical methods for the in vitro reconstitution of the tubulin code and integrates these with structural, proteomic, microscopy-based approaches and modeling to elucidate how the tubulin code regulates microtubule function in health and disease at scales ranging from interactions between single atoms in proteins to the behavior of cells. Many anticancer therapeutics used widely in the clinic target microtubules directly. Our work aims to elucidate the functions of the tubulin code in cell physiology, and also leverages this knowledge for the identification of new targets and approaches for therapeutic intervention.
Last reviewed on January 17, 2023