Abstract
Actin networks and actin-binding proteins (ABPs) are most abundant in the cytoskeleton of neurons. The function of ABPs in neurons is nucleation of actin polymerization, polymerization or depolymerization regulation, bundling of actin through crosslinking or stabilization, cargo movement along actin filaments, and anchoring of actin to other cellular components. In axons, ABP–actin interaction forms a dynamic, deep actin network, which regulates axon extension, guidance, axon branches, and synaptic structures. In dendrites, actin and ABPs are related to filopodia attenuation, spine formation, and synapse plasticity. ABP phosphorylation or mutation changes ABP–actin binding, which regulates axon or dendritic plasticity. In addition, hyperactive ABPs might also be expressed as aggregates of abnormal proteins in neurodegeneration. Those changes cause many neurological disorders. Here, we will review direct visualization of ABP and actin using various electron microscopy (EM) techniques, super resolution microscopy (SRM), and correlative light and electron microscopy (CLEM) with discussion of important ABPs in neuron.
Highlights
Neurons are specialized cells with long processes or connections in the nervous system
We focused on the application of (1) electron microscopy (EM) such as single particle analysis, electron tomography, unroofing and, etching with cryo-techniques, (2) super resolution microscopy (SRM) such as stochastic optical reconstruction microscopy (STORM), photo-activated localization microscopy (PALM), and stimulated emission depletion (STED), (3) correlative light and electron microscopy (CLEM) to the study of the molecular architecture of actin and actin-binding proteins (ABPs), since these are the most widely used techniques for such molecular ultrastructural studies
The temporally separated individual molecules are localized with high precision, and a super-resolution image can be constructed from the collections of localizations from multiple fluorophores. This method enables the visualization of the ultrastructure of actin and ABP that was previously inaccessible with conventional optical methods and EM (Xu et al, 2013; Zhong et al, 2014; Sidenstein et al, 2016; Han et al, 2017; Pan et al, 2018; Wang G. et al, 2019)
Summary
Neurons are specialized cells with long processes or connections in the nervous system. Each neuron has two types of cytoplasmic protrusions from the neuronal cell body, an axon and a dendrite (Figure 1). Because each neuron has a single axon, axon dysfunction is both the result and the main cause of many neurological disorders, such as loss of cognitive ability, general paralysis, paraplegia, and loss of sensory function. Another protrusion from neuron is dendrites, and the main function is receiving signals from other neurons. Dynamic regulation of actin polymerization and organization mediates axon morphogenesis and path finding to synaptic targets. Actin filaments do not function in a naked state, and actin binding proteins (ABP) s regulate all aspects of actin, that is, actin filament dynamics and
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