KATNAL1 is a more active and stable isoform of katanin, and is expressed dominantly in neurons

Microtubule severing is essential for reorganization of microtubules during neuronal migration and process elongation. Katanin is a microtubule-severing enzyme, of which the major catalytic subunits are katanin A1 (KATNA1) and katanin A-like 1 (KATNAL1). The domain organization of the two subunits are almost the same; however, little is known about their functional difference. Here, we compared the expression pattern, microtubule-severing activity, intracellular degradation and knockdown phenotype in cultured cells of the two subunits. While KATNA1 was expressed ubiquitously among tissues of young adult mice, KATNAL1 was highly expressed in the brain and the testis. Neurons expressed almost only KATNAL1. When introduced into Neuro2a cells, KATNAL1 showed higher microtubule-severing activity. Cycloheximide chase analysis revealed that KATNAL1 is more stable in cells. To elucidate which part of the molecules are responsible for these characteristics, we generated chimeric molecules by swapping the amino-terminal and carboxyl-terminal halves between the two subunits. Experiments using these chimeras revealed that the amino-terminal half region is the determinant for their characteristics. Furthermore, KATNAL1 knockdown in Neuro2a cells resulted in enhancement of process elongation, while KATNA1 knockdown showed no effect. These data suggest that more active and more stable katanin subunit, KATNAL1, plays more important role in process elongation. (C) 2018 Elsevier Inc. All rights reserved.