Microtubule-severing enzymes at the cutting edge

Abstract

Summary ATP-dependent severing of microtubules was first reported in Xenopus laevis egg extracts in 1991. Two years later this observation led to the purification of the first known microtubule-severing enzyme, katanin. Katanin homologs have now been identified throughout the animal kingdom and in plants. Moreover, members of two closely related enzyme subfamilies, spastin and fidgetin, have been found to sever microtubules and might act alongside katanins in some contexts (Roll-Mecak and McNally, 2010;Yu et al., 2008;Zhang et al., 2007). Over the past few years, it has become clear that microtubule-severing enzymes contribute to a wide range of cellular activities including mitosis and meiosis, morphogenesis, cilia biogenesis and disassembly, and migration. Thus, this group of enzymes is revealing itself to be among the most important of the microtubule regulators. This Commentary focuses on our growing understanding of how microtubule-severing enzymes contribute to the organization and dynamics of diverse microtubule arrays, as well as the structural and biophysical characteristics that afford them the unique capacity to catalyze the removal of tubulin from the interior microtubule lattice. Our goal is to provide a broader perspective, focusing on a limited number of particularly informative, representative and/or timely findings.

Microtubule nucleation and organization in dendrites

“…32,36 Microtubule fragment seeds are generated when microtubule-severing enzymes break up preexisting microtubules. 37,38 Evidence that microtubule fragment-based nucleation occurs in dendrites comes from the genetic disruption of severing enzymes Spastin, Katanin 60 and Katanin p60-like1, all of which are required for correct dendrite patterning. [39][40][41][42] Moreover, loss of Katanin p60-like1 reduces the frequency of microtubule polymerization events in the terminal branches of class IV neurons.…”

A novel family of katanin-like 2 protein isoforms (KATNAL2), interacting with nucleotide-binding proteins Nubp1 and Nubp2, are key regulators of different MT-based processes in mammalian cells

“…In parallel, a lot has been learned about additional mechanisms underlying MT plasticity. Following the initial discovery of katanin [7], the uncovering of a still expanding superfamily of proteins with MTsevering activity that can introduce breaks into the polymer lattice and generate shorter MT fragments, has provided some understanding on how existing MT architecture can be modified and re-modeled locally or how structures can be organized de novo using such released MT fragments, sometimes transported to other intracellular domains, as seeds [8][9][10][11].…”

KATNB1 in the human testis and its genetic variants in fertile and oligoasthenoteratozoospermic infertile men

“…Katanin is an evolutionary conserved microtubule-severing complex, consisting of a p60 enzyme subunit (encoded by the Katna1 gene) and a p80 accessory protein subunit (encoded by the Katnb1 gene) that is thought to regulate microtubule-severing targeting and activity (McNally & Vale, 1993;Hartman et al, 1998;McNally et al, 2000;Roll-Mecak & McNally, 2010;Sharp & Ross, 2012). Katanin binds to microtubules and, upon ATP hydrolysis, undergoes a conformational change to de-stabilize tubulin-tubulin contacts within the microtubule lattice, leading to microtubule severing (Roll-Mecak & McNally, 2010;Sharp & Ross, 2012). Katanin can sever microtubules along their length or at their ends to control number and stability (Roll-Mecak & McNally, 2010;Baas & Sharma, 2011;Sharp & Ross, 2012).…”