Abstract
Neurons transmit and receive information at specialized junctions called synapses. Excitatory synapses form at the junction between a presynaptic axon terminal and a postsynaptic dendritic spine. Supporting the shape and function of these junctions is a complex network of actin filaments and its regulators. Advances in microscopic techniques have enabled studies of the organization of actin at synapses and its dynamic regulation. In addition to highlighting recent advances in the field, we will provide a brief historical perspective of the understanding of synaptic actin at the synapse. We will also highlight key neuronal functions regulated by actin, including organization of proteins in the pre- and post- synaptic compartments and endocytosis of ion channels. We review the evidence that synapses contain distinct actin pools that differ in their localization and dynamic behaviors and discuss key functions for these actin pools. Finally, whole exome sequencing of humans with neurodevelopmental and psychiatric disorders has identified synaptic actin regulators as key disease risk genes. We briefly summarize how genetic variants in these genes impact neurotransmission via their impact on synaptic actin.
Highlights
The neuronal synapse is the elemental component of communication in the nervous system and is composed of both pre- and post-synaptic compartments
Dynamic changes in actin power formation of dendritic filopodia and their elaboration into dendritic spines Morphological changes of spines influenced by sensory input and links between actin, its regulators and spine formation, structural plasticity and function Changes of the spine neck, spine size and actin-binding proteins are correlated with synaptic strength Actin dynamics impact receptor trafficking, recycling and anchoring between synaptic and nonsynaptic zones postsynaptic density (PSD) protein reorganization is driven by changes in actin polymerization Actin remodeling promotes microtubule entry into dendritic spines
Actin monomers assemble into highly complex networks of actin filaments, under the direction of many diverse actin regulatory proteins
Summary
The neuronal synapse is the elemental component of communication in the nervous system and is composed of both pre- and post-synaptic compartments. Siliconerhodamine desbromo-desmethyl-jasplakinolide (SiR-actin) was created as an alternative to Lifeact for these approaches and has since been used in live imaging STED to visualize the periodic actin structures in dendritic spine necks (see Section 4.1) [30,31,32] These studies provided some of the earliest evidence that the actin cytoskeleton may underlie functional and structural changes of the synapse. A more tractable and accessible technique for future lines of research on the actin cytoskeleton and its regulatory proteins may be expansion microscopy [33,34], which allows for the visualization of small, typically diffraction limited, structures by physical magnification The basis of this method is to polymerize an acrylamide gel within a cell or tissue, and crosslinking endogenous proteins to that gel. Our review will explore seminal findings and discuss ongoing and future challenges in the field
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