An MBoC Favorite: Role of GTP hydrolysis in microtubule dynamics: information from a slowly hydrolyzable analogue, GMPCPP

Abstract

In celebration of MBoC’s first 20 years, members of the Editorial Board, members of the ASCB Council, and others comment on their favorite MBoC papers from the past two decades. Admirers of mitosis delight in viewing the dynamicity of microtubules during mitosis, so it is no surprise that the properties required for such dynamicity—termed “dynamic instability”—has been a major research focus since the mid-20th century. To study the role of GTP in the dynamic instability of microtubules, investigators have used different GTP analogues. In general, GTP that binds tubulin is stable in the microtubule lattice, but it becomes unstable when hydrolyzed to GDP-tubulin. Hyman et al. (1992) showed that the GTP analogue guanylyl(α,β)-methylene-diphosphonate (GMPCPP) was more stable than GTP and promoted polymerization, because it was hydrolyzed extremely slowly, making it almost equivalent to a nonhydrolyzable analogue. The authors concluded that GTP hydrolysis is not important for microtubule polymerization but is essential for microtubule depolymerization and, therefore, microtubule dynamics. They also noticed that GMPCPP hydrolysis was enhanced by the surrounding GTP lattice, identifying cooperativity as another key element in dynamic instability. Since the appearance of this article, our understanding of dynamic instability has continued to improve and evolve. A PDF file of the paper discussed above is attached to this article.