Microtubule-severing protein Katanin regulates neuromuscular junction development and dendritic elaboration in Drosophila
Microtubule-severing protein Katanin regulates neuromuscular junction development and dendritic elaboration in Drosophila
复制标题
微管切断蛋白剑宁调节果蝇神经肌肉接头发育和树突精细化
DOI：
10.1242/dev.097774
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发表时间：
2014-03-01
期刊：
影响因子：
4.6
通讯作者：
Jin, Shan
中科院分区：
文献类型：
--
作者：
Mao, Chuan-Xi;Xiong, Ying;Jin, Shan
微管在细胞分裂、细胞生长和运动、细胞内运输和维持细胞形状等生物学过程中起着重要作用。MT异常与神经发育和神经退行性疾病如遗传性痉挛性截瘫有关。在许多MT调节因子中，katanin是第一个被鉴定的MT切断蛋白，但其神经元功能尚未在多细胞生物中被检测。Katanin由两个亚基组成;催化亚基Katanin 60含有AAA（与多种细胞活性相关的ATP酶）结构域，并在水解ATP时破坏MT纤维，而Katanin 80是靶向和调节亚基。为了剖析Katanin的体内功能，我们在果蝇Katanin 60中产生突变，并以组织特异性方式操纵其表达。Katanin 60的突变体对蛹是致命的，这表明它对生存力是必不可少的。Katanin 60的功能丧失突变体表现出过多的卫星终扣，神经传递效率降低，神经肌肉接头处的脑池扩大。在外周感觉神经元中，Katanin 60的缺失导致树突的精细化增加，而Katanin 60的过度表达导致相反的结果。遗传相互作用分析表明，MT乙酰化水平的增加了其对Katanin介导的神经元和非神经元系统切断的易感性。总之，我们的研究结果首次证明Katanin 60是神经肌肉突触和树突正常发育所必需的。
Microtubules (MTs) are crucial for diverse biological processes including cell division, cell growth and motility, intracellular transport and the maintenance of cell shape. MT abnormalities are associated with neurodevelopmental and neurodegenerative diseases such as hereditary spastic paraplegia. Among many MT regulators, katanin was the first identified MT-severing protein, but its neuronal functions have not yet been examined in a multicellular organism. Katanin consists of two subunits; the catalytic subunit katanin 60 contains an AAA (ATPases associated with a variety of cellular activities) domain and breaks MT fibers while hydrolyzing ATP, whereas katanin 80 is a targeting and regulatory subunit. To dissect the in vivo functions of Katanin, we generated mutations in Drosophila Katanin 60 and manipulated its expression in a tissue-specific manner. Null mutants of Katanin 60 are pupal lethal, demonstrating that it is essential for viability. Loss-of-function mutants of Katanin 60 showed excess satellite boutons, reduced neurotransmission efficacy, and more enlarged cisternae at neuromuscular junctions. In peripheral sensory neurons, loss of Katanin 60 led to increased elaboration of dendrites, whereas overexpression of Katanin 60 resulted in the opposite. Genetic interaction analyses indicated that increased levels of MT acetylation increase its susceptibility to Katanin-mediated severing in neuronal and non-neuronal systems. Taken together, our results demonstrate for the first time that Katanin 60 is required for the normal development of neuromuscular synapses and dendrites.