Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland.
Core Facility, International Institute of Molecular and Cell Biology, 02-109, Warsaw, Poland.
Mol Neurobiol. 2019 Jul;56(7):4866-4879. doi: 10.1007/s12035-018-1418-9. Epub 2018 Nov 7.
The proper shape of dendritic arbors of different types of neurons determines their proper communication within neuronal networks. The shape of dendritic arbors is acquired during a complex and multistep process called dendritogenesis. In most cases, once proper morphology is achieved, it remains stable throughout the lifespan, with the exception of rare events during which dendrites are abruptly pruned. The endosomal sorting complex required for transport (ESCRT) is multisubunit machinery that is involved in various cellular processes when membrane scission is needed. ESCRT subcomplexes regulate dendrite pruning in Drosophila neurons. However, the contribution of ESCRT components to the dendritogenesis of mammalian neurons and control of dendrite stability remains poorly defined. In the present study, we found that ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III and Vps4 are required for proper dendrite morphology under basal culture conditions and for accelerated dendritogenesis in response to phosphoinositide 3-kinase (PI3K) activation. The knockdown of Vps28 (ESCRT-I) and Vps25 (ESCRT-II) resulted in downregulation of the activity of mechanistic/mammalian target of rapamycin complex 1. We also demonstrated that Vps28, Vps24, and Vps25 are required for dendrite stabilization in mature neurons.
不同类型神经元树突棘的适当形状决定了它们在神经元网络中的适当交流。树突棘的形状是在一个复杂的多步骤过程中获得的,这个过程称为树突发生。在大多数情况下,一旦获得适当的形态,它在整个生命周期中保持稳定,除了在极少数情况下树突会突然修剪。需要进行膜分裂时,内体分选复合物需要运输(ESCRT)是一种多亚基机制,涉及多种细胞过程。ESCRT 亚复合物调节果蝇神经元中的树突棘修剪。然而,ESCRT 成分对哺乳动物神经元的树突发生和树突稳定性的控制的贡献仍未得到很好的定义。在本研究中,我们发现 ESCRT-0、ESCRT-I、ESCRT-II 和 ESCRT-III 和 Vps4 在基础培养条件下对适当的树突形态和对磷酸肌醇 3-激酶(PI3K)激活的加速树突发生是必需的。Vps28(ESCRT-I)和 Vps25(ESCRT-II)的敲低导致机械/雷帕霉素靶蛋白复合物 1 的活性下调。我们还证明 Vps28、Vps24 和 Vps25 是成熟神经元中树突稳定所必需的。