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Cited by 4Microtubule and mitosis dynamicsCancer Treatment and PharmacologyGenetic and Kidney Cyst Diseases

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A tubulin-binding protein that preferentially binds to GDP-tubulin and promotes GTP exchange

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Yon, Wesley J., Ha, Taekjip, Zheng, Yixian, Pedersen, Ross T.A.·2025·Journal of Biological Chemistry
DOI 10.1016/j.jbc.2025.110401PMC PMC12302650

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Abstract

α- and β-tubulin form heterodimers, with GTPase activity, that assemble into microtubules. Like other GTPases, the nucleotide-bound state of tubulin heterodimers controls whether the molecules are in a biologically active or inactive state. While α-tubulin in the heterodimer is constitutively bound to GTP, β-tubulin can be bound to either GDP (GDP-tubulin) or GTP (GTP-tubulin). GTP-tubulin hydrolyzes its GTP to GDP following assembly into a microtubule and, upon disassembly, must exchange its bound GDP for GTP to participate in subsequent microtubule polymerization. Tubulin dimers have been shown to exhibit rapid intrinsic nucleotide exchange in vitro, leading to a commonly accepted belief that a tubulin guanine nucleotide exchange factor (GEF) may be unnecessary 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.

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Metadata

Authors
Yon, W. J., Ha, T., Zheng, Y., & Pedersen, R. T. A.
Affiliations
  • Johns Hopkins University (US)
  • Boston Children's Hospital (US)
  • Carnegie Institution for Science (US)
Corresponding author
Zheng, Yixian
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2025-08
Volume
301
Issue
8
Pages
110401
ISSN
0021-9258 (ISSN-L)
DOI
10.1016/j.jbc.2025.110401
PMC
PMC12302650
OpenAlex
W4411443056
Cited by
4
References
1
Citations by year
2026: 4
FWCI
2.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • Johns Hopkins University
  • National Institutes of Health
  • NIH National Institute of General Medical Sciences (GM110151, R35 GM122569, F32 GM142145, GM106023)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
Keywords
GDP-tubulin, tubulin heterodimers, nucleotide exchange, microtubule assembly, microtubule disassembly, spindle assembly, GTP hydrolysis

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