Beyond uniformity: Exploring the heterogeneous and dynamic nature of the microtubule lattice

A fair amount of research on microtubules since their discovery in 1963 has focused on their dynamic tips. In contrast, the microtubule lattice was long believed to be highly regular and static, and consequently received far less attention. Yet, as it turned out, the microtubule lattice is neither as regular, nor as static as previously believed: structural studies uncovered the remarkable wealth of different conformations the lattice can accommodate. In the last decade, the microtubule lattice was shown to be labile and to spontaneously undergo renovation, a phenomenon that is intimately linked to structural defects and was called “microtubule self-repair". Following this breakthrough discovery, further recent research provided a deeper understanding of the lattice self-repair mechanism, which we review here. Instrumental to these discoveries were in vitro microtubule reconstitution assays, in which microtubules are grown from the minimal components required for their dynamics. In this review, we propose a shift from the term “lattice self-repair” to “lattice dynamics”, since this phenomenon is an inherent property of microtubules and can happen without microtubule damage. We focus on how in vitro microtubule reconstitution assays helped us learn (1) which types of structural variations microtubules display, (2) how these structural variations influence lattice dynamics and microtubule damage caused by mechanical stress, (3) how lattice dynamics impact tip dynamics, and (4) how microtubule-associated proteins (MAPs) can play a role in structuring the lattice. Finally, we discuss the unanswered questions about lattice dynamics and how technical advances will help us tackle these questions.