F-actin patches associated with glutamatergic synapses control positioning of dendritic lysosomes.

Bas Van Bommel,Marina Mikhaylova,Julia Bär,Oliver Kobler,Anja Konietzny

doi:10.15252/embj.2018101183

Bas Van Bommel, Marina Mikhaylova + Show 3 more

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https://doi.org/10.15252/embj.2018101183

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Abstract

Organelle positioning within neurites is required for proper neuronal function. In dendrites, with their complex cytoskeletal organization, transport of organelles is guided by local specializations of the microtubule and actin cytoskeleton, and by coordinated activity of different motor proteins. Here, we focus on the actin cytoskeleton in the dendritic shaft and describe dense structures consisting of longitudinal and branched actin filaments. These actin patches are devoid of microtubules and are frequently located at the base of spines, or form an actin mesh around excitatory shaft synapses. Using lysosomes as an example, we demonstrate that the presence of actin patches has a strong impact on dendritic organelle transport, as lysosomes frequently stall at these locations. We provide mechanistic insights on this pausing behavior, demonstrating that actin patches form a physical barrier for kinesin‐driven cargo. In addition, we identify myosin Va as an active tether which mediates long‐term stalling. This correlation between the presence of actin meshes and halting of organelles could be a generalized principle by which synapses control organelle trafficking.

Highlights

The ability of neurons to convey and store information is based on their intricate and complex architecture, which allows a multitude of synaptic cell-to-cell contacts
We show that the filamentous actin (F-actin) mesh acts both as a passive, physical barrier, slowing down transport of vesicles driven by MT motors, and as an anchoring point for active stalling of vesicles via myosins
The organization and functional relevance of the actin cytoskeleton in dendritic shafts of mature hippocampal neurons has not been investigated in much detail so far

Summary

Introduction

The ability of neurons to convey and store information is based on their intricate and complex architecture, which allows a multitude of synaptic cell-to-cell contacts. The most studied and most prevalent type of synaptic contacts is excitatory spine synapses, which are located on small dendritic protrusions called spines. Actin in the spine has been the focus of extensive research efforts, and various functions of filamentous actin (F-actin) in dendritic spines have been described in detail (Matus, 2000; Korobova & Svitkina, 2010; Svitkina et al, 2010; Kim et al, 2015; Bar et al, 2016; Hlushchenko et al, 2016; Mikhaylova et al, 2018). Actin dynamics are instrumental for activity-dependent structural plasticity of dendritic spines (Matsuzaki et al, 2004; Racz & Weinberg, 2013; Bosch et al, 2014; Kim et al, 2015; Mikhaylova et al, 2018). In addition to synapses located on spines, there is a smaller fraction of glutamatergic synapses formed directly on the dendritic shaft, but their contribution to neuronal function is investigated to a lesser extent (Bourne & Harris, 2011; Reilly et al, 2011)

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