Department of Molecular Neurogenetics, ZMNH, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251, Hamburg, Germany.
RG Neuroplasticity, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany.
Sci Rep. 2019 Nov 4;9(1):15940. doi: 10.1038/s41598-019-52367-3.
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.
微管切割调节细胞骨架重排，从而支撑各种细胞功能。Katanin 是一种异二聚体，由催化亚基（p60）和调节亚基（p80）组成，可切割动态微管，从而调节细胞分裂的多个阶段。然而，p60 katanin 在哺乳动物大脑中对于胚胎和成年神经发生的作用还知之甚少。在本研究中，我们生成了 Katna1 敲除小鼠，并发现与 katanin 在有丝分裂中的关键作用一致，组成型纯合 Katna1 缺失是致命的。Katanin p60 杂合不足导致皮质发生过程中室下区神经元祖细胞积累，并损害成年海马齿状回（DG）颗粒下区的增殖。这并没有损害 DG 的可塑性或空间和情景学习记忆任务，与成年神经发生可能与海马依赖认知过程的特定形式有关的解释一致。我们的数据表明，微管切割蛋白 katanin p60 在体内调节胚胎发育和成年神经发生过程中神经元祖细胞的增殖方面起着关键作用。
