Models, Regulations, and Functions of Microtubule Severing by Katanin

Abstract

Regulation of microtubule dynamics depends on stochastic balance between polymerization and severing process which lead to differential spatiotemporal abundance and distribution of microtubules during cell development, differentiation, and morphogenesis. Microtubule severing by a conserved AAA family protein Katanin has emerged as an important microtubule architecture modulating process in cellular functions like division, migration, shaping and so on. Regulated by several factors, Katanin manifests connective crosstalks in network motifs in regulation of anisotropic severing pattern of microtubule protofilaments in cell type and stage dependent way. Mechanisms of structural disintegration of microtubules by Katanin involve heterogeneous mechanochemical processes and sensitivity of microtubules to Katanin plays significant roles in mitosis/meiosis, neurogenesis, cilia/flagella formation, cell wall development and so on. Deregulated and uncoordinated expression of Katanin has been shown to have implications in pathophysiological conditions. In this paper, we highlight mechanistic models and regulations of microtubule severing by Katanin in context of structure and various functions of Katanin in different organisms.

Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors

“…During mitosis, anaphase chromatid-to-pole motion is tightly linked to de-polymerization of the opposite ends of chromosome-associated microtubules. Synchronized microtubule dynamics result from the highly regulated, concerted action of several proteins, including kat60 (Ghosh et al, 2012; Zhang et al, 2007). Since kat80 is important for targeting the kat60 catalytic subunit, our observation of delayed onset of anaphase in kat80-IR NBs demonstrates the central role of katanin in anaphase.…”

The cytoskeleton and neurite initiation

“…It is also important to note that the presence of microtubule binding proteins such as Tau or specific posttranslational modifications such as acetylation and polyglutamylation can inhibit or facilitate microtubule severing by spastin and katanin, respectively. 192 Overall, the data suggest that a balance of microtubule bundling, dynamics and stability is required for neuritogenesis. The neuron-specific expression of various microtubule bundling proteins, such as canonical type I (Map1B) and type II (Map2, Tau) Maps as well as DCX and LIS1, are indicative of a necessity to regulate the organization of microtubule bundles during neuronal morphogenesis.…”

“…140,191 Although their exact mechanism of action is unknown, katanin is postulated to bind to the sides of microtubules and uses ATP hydrolysis to cause structural bending of the microtubule lattice and remove microtubule dimers eventually leading to severing. 192 Microtubule severing by spastin and katanin generate short microtubules, which can be reconfigured and transported more easily to respond to environmental signals and alter microtubule organization. It is also important to note that the presence of microtubule binding proteins such as Tau or specific posttranslational modifications such as acetylation and polyglutamylation can inhibit or facilitate microtubule severing by spastin and katanin, respectively.…”

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].…”