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

Marcelina Firkowska,Jacek Jaworski,Matylda Macias

doi:10.1007/s12035-018-1418-9

Marcelina Firkowska, Jacek Jaworski + Show 1 more

Open Access

https://doi.org/10.1007/s12035-018-1418-9

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Abstract

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.

Highlights

Dendrites are a compartment of neurons that specialize in receiving and computing synaptic inputs from other cells within a given neuronal network
The endosomal sorting complex required for transport (ESCRT) is a multisubunit machinery that is mostly known for its role in generating multivesicular bodies (MVBs; i.e., membranous compartments that are critical for sorting endocytosed cargo for lysosomal degradation) [3, 4]
We found that ESCRT-I, ESCRT-II, and ESCRT-III and Vps4 are needed for phosphoinositide 3-kinase (PI3K)-induced, mechanistic/ mammalian target of rapamycin-dependent dendritogenesis

Summary

Introduction

Dendrites are a compartment of neurons that specialize in receiving and computing synaptic inputs from other cells within a given neuronal network. Some neurons possess only a single dendrite, whereas other neurons develop many dendrites and form very complex dendritic arbors. Both the genetic program and extracellular environment impact the final shape of dendritic arbors [1]. The ESCRT as a whole complex or its subcomplexes are important for the formation of exosomes and microvesicles, virus budding, abscission of the intercellular bridge during cytokinesis, nuclear envelope reformation, repair, quality control, and repair of the plasma membrane [5]. An additional role for ESCRT was described in neurons, in which it severs proximal dendrites during the dendrite pruning of dendritic arborization (da) neurons in Drosophila at the time of pupae metamorphosis [6, 7]. An additional protein that is needed for proper ESCRT function is VPS4, an adenosine

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