title: The structured core of human β tubulin confers isotype-specific polymerization properties.
abstract: Diversity in cytoskeleton organization and function may be achieved through variations in primary sequence of tubulin isotypes. Recently, isotype functional diversity has been linked to a "tubulin code" in which the C-terminal tail, a region of substantial sequence divergence between isotypes, specifies interactions with microtubule-associated proteins. However, it is not known whether residue changes in this region alter microtubule dynamic instability. Here, we examine recombinant tubulin with human β isotype IIB and characterize polymerization dynamics. Microtubules with βIIB have catastrophe frequencies approximately threefold lower than those with isotype βIII, a suppression similar to that achieved by regulatory proteins. Further, we generate chimeric β tubulins with native tail sequences swapped between isotypes. These chimeras have catastrophe frequencies similar to that of the corresponding full-length construct with the same core sequence. Together, our data indicate that residue changes within the conserved β tubulin core are largely responsible for the observed isotype-specific changes in dynamic instability parameters and tune tubulin's polymerization properties across a wide range.
authors.affiliation: Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, NY 10065.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Pamula
authors.affiliation: Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, NY 10065.
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Ti
authors.affiliation: Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, NY 10065 kapoor@rockefeller.edu.
authors.forename: Tarun M
authors.initials: TM
authors.lastname: Kapoor
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D058105:Polymerization; D014404:Tubulin / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; D014404:Tubulin