How tubulin and kinesin gene families specialize microtubule networks

ABSTRACT
Our understanding of the inventory of genetically encoded and post-translationally modified forms of cytoskeletal
proteins has grown immensely over the last 20 years. It is now clear that microtubule networks are not uniform
tracks that are traversed by a common set of motor proteins. Instead, the tubulin subunits of microtubules can
sample a variety of structural and biochemical states, creating the potential for molecularly distinct microtubule
tracks that are specific to different cell types, or even specific to different compartments of the same cell.
Similarly, the large family of kinesin genes and even larger family of kinesin proteoforms creates potential for
distinct modes of transport and force generation along microtubules. Understanding of how cells use these
inventories to create a range of specific biological outcomes now represents a critical knowledge gap in
cytoskeletal biology. This project will address two major knowledge gaps that are critical for the tubulin code
model, and also broadly important for the microtubule field: 1) the mechanistic role(s) of tubulin isotypes in
generating programs of tubulin PTMs, and 2) expanding the inventory of MAPs that read the tubulin code and
understanding how reading impacts function.