Journal of Biological Chemistry

α- and β-tubulin form GTPase heterodimers and assemble into microtubules. Like other GTPases, the tubulin heterodimer's nucleotide-bound state regulates its activity. In the dimer, α-tubulin is constitutively bound to GTP, while β-tubulin can bind to either GDP (GDP-tubulin) or GTP (GTP-tubulin). Following assembly into microtubules, GTP-tubulin hydrolyzes GTP to GDP, triggering microtubule disassembly. This generates free GDP-tubulin, which must exchange GDP for GTP to undergo assembly again. Tubulin dimers undergo rapid nucleotide exchange in vitro, leading to a commonly accepted belief that a tubulin guanine nucleotide exchange factor (GEF) may be unnecessary for microtubule assembly in cells. Here, we use quantitative binding assays to show that BuGZ, a spindle assembly factor, binds tightly to GDP-tubulin, less tightly to GTP-tubulin, and weakly to microtubules. We further show that BuGZ promotes the incorporation of GTP into tubulin using a nucleotide exchange assay. The discovery of a tubulin GEF suggests a mechanism that may aid rapid microtubule assembly dynamics in cells.

GTPase

guanine nucleotide exchange factor (GEF)

microtubule

microtubule-associated protein (MAP)

tubulin

Bub3-interacting and GLEBS motif-containing protein ZNF207

guanine nucleotide exchange factor

guanosine triphosphate

Proline-Rich Region 2

© 2025 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biologyé