Dynamic microtubules at the synapse

Abstract

Microtubules (MTs) are a fundamental cytoskeletal component that give neurons structure and are the primary polymer system for long distance transport of cargo throughout the cytoplasm. Although neurons are highly polarized and their structure is often maintained throughout the life of an organism, MTs can remain dynamic in axons and dendrites, undergoing bouts of polymerization and depolymerization, referred to as dynamic instability. Furthermore, MTs can be nucleated outside of the centrosome or MT organizing center (MTOC) that is located in the cell body, allowing dynamic formation and branching of MT polymers throughout the neuron. Together, these recent findings point to a much more dynamic landscape of microtubules in developing and mature neurons than was previously appreciated. Here we will focus on recent studies that show MT dynamics are playing a role at the synapse, both post-synaptically in dendrites and pre-synaptically in axons.

Figure 1.. Dynamic microrubules play important roles both presynaptically and postsynaptically.

Presynaptically in the axon, microtubules preferentially nucleate via the augmin/gamma-tubulin complex as well as concentrate their plus ends in the en passant dialation termed the synaptic bouton. Both synaptic vesicles and dense core vesicles are transported along microtubules by the motor protein KIF1A and concentrate at boutons. Postsynaptically in the dendrite, microtubules polymerize directly into the dendritic spine and transport vesicles via KIF1A as well. Microtubule polymerization into the dendritic spine is dependent on filamentous actin (F-actin) concentrating at the base of spines.

Figure 2.. Microtubules associate with multiple components at the Drosophila neuromuscular junction

A number of recent studies have shown that there is a complex of proteins, including Futsch/MAP1B, Ankyrin proteins (Ankyrin2-L, Ankyrin2-XL), and formin proteins (DAAM shown, Dia not shown) that associate with microtubules and with active zones (shown as red circles of bruchpilot (Brp)). These proteins appear to be important for organizing synaptic architecture, regulating synaptic microtubules and potentially guiding the delivery of synaptic vesicles to active zones. Synaptic vesicles and actin are not shown for simplicity. Microtubules are shown as continuous structures but are likely bundles of shorter dynamic microtubules.