ESCRT Proteins Control the Dendritic Morphology of Developing and Mature Hippocampal Neurons

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-018-1418-9) contains supplementary material, which is available to authorized users.