Reinterpreting the effects of α-tubulin K40 acetylation on microtubule stability and cellular functions.

Abstract

Acetylation of α-tubulin at lysine 40 (K40) has been studied in many model organisms for decades, mainly by manipulating levels of deacetylase and acetyltransferase enzymes, such as the α-tubulin acetyltransferase MEC-17 (also known as ATAT1). Observations that acetylation accumulates in some long-lived microtubules and that MEC-17 is important for maintaining microtubule organization and key cellular functions have led to the prevailing view that K40 acetylation stabilizes and protects microtubules, although many questions about its precise function remain. Recent gene editing of endogenous α-tubulin and in vitro microtubule polymerization assays have indicated that K40 acetylation itself does not maintain microtubule structure as MEC-17 does, but rather negatively regulates specific aspects of microtubule dynamics (i.e. nucleation and shrinkage but not elongation) and slightly impairs neuronal extension. This Opinion article discusses multiple important studies on α-tubulin K40 acetylation that have shaped our understanding of its function since its discovery in the 1980s, with the aim of clarifying the actual role of this major tubulin post-translational modification.