The Microtubule Severing Protein Katanin Regulates Proliferation of Neuronal Progenitors in Embryonic and Adult Neurogenesis

Franco L. Lombino, Mary Muhia, Jeffrey Lopez-Rojas, Monika S. Brill, Edda Thies, Laura Ruschkies, David Lutz, Melanie Richter, Torben J. Hausrat, André T. Lopes, Francis J. McNally, Irm Hermans-Borgmeyer, Jessica E.M. Dunleavy, Sabine Hoffmeister-Ullerich, Michael Frotscher, Thomas Misgeld, Michael R. Kreutz, Froylan Calderon de Anda, Matthias Kneussel

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Microtubule severing regulates cytoskeletal rearrangement underlying various cellular functions. Katanin, a heterodimer, consisting of catalytic (p60) and regulatory (p80) subunits severs dynamic microtubules to modulate several stages of cell division. The role of p60 katanin in the mammalian brain with respect to embryonic and adult neurogenesis is poorly understood. Here, we generated a Katna1 knockout mouse and found that consistent with a critical role of katanin in mitosis, constitutive homozygous Katna1 depletion is lethal. Katanin p60 haploinsufficiency induced an accumulation of neuronal progenitors in the subventricular zone during corticogenesis, and impaired their proliferation in the adult hippocampus dentate gyrus (DG) subgranular zone. This did not compromise DG plasticity or spatial and contextual learning and memory tasks employed in our study, consistent with the interpretation that adult neurogenesis may be associated with selective forms of hippocampal-dependent cognitive processes. Our data identify a critical role for the microtubule-severing protein katanin p60 in regulating neuronal progenitor proliferation in vivo during embryonic development and adult neurogenesis.

Original languageEnglish
Article number15940
Number of pages12
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Cite this

Lombino, F. L., Muhia, M., Lopez-Rojas, J., Brill, M. S., Thies, E., Ruschkies, L., Lutz, D., Richter, M., Hausrat, T. J., Lopes, A. T., McNally, F. J., Hermans-Borgmeyer, I., Dunleavy, J. E. M., Hoffmeister-Ullerich, S., Frotscher, M., Misgeld, T., Kreutz, M. R., de Anda, F. C., & Kneussel, M. (2019). The Microtubule Severing Protein Katanin Regulates Proliferation of Neuronal Progenitors in Embryonic and Adult Neurogenesis. Scientific Reports, 9(1), [15940]. https://doi.org/10.1038/s41598-019-52367-3