The Actin/Spectrin Membrane-Associated Periodic Skeleton in Neurons.

Nicolas Unsain,Fernando D Stefani,Alfredo Cáceres

doi:10.3389/fnsyn.2018.00010

Abstract

Neurons are the most asymmetric cell types, with their axons commonly extending over lengths that are thousand times longer than the diameter of the cell soma. Fluorescence nanoscopy has recently unveiled that actin, spectrin and accompanying proteins form a membrane-associated periodic skeleton (MPS) that is ubiquitously present in mature axons from all neuronal types evaluated so far. The MPS is a regular supramolecular protein structure consisting of actin “rings” separated by spectrin tetramer “spacers”. Although the MPS is best organized in axons, it is also present in dendrites, dendritic spine necks and thin cellular extensions of non-neuronal cells such as oligodendrocytes and microglia. The unique organization of the actin/spectrin skeleton has raised the hypothesis that it might serve to support the extreme physical and structural conditions that axons must resist during the lifespan of an organism. Another plausible function of the MPS consists of membrane compartmentalization and subsequent organization of protein domains. This review focuses on what we know so far about the structure of the MPS in different neuronal subdomains, its dynamics and the emerging evidence of its impact in axonal biology.

Highlights

Plasma membrane domain specialization is determinant for key cellular activities such as adhesion, signaling, membrane excitability, endo/exocytosis and stress resistance, among others
The resemblance to the erythrocyte membrane-cortical cytoskeleton (EMCC) components, together with the distance between F-actin rings equivalent to the size of a stretched spectrin tetramer, supported the conception of a structural working model of the membrane-associated periodic skeleton (MPS), which has been corroborated and improved by others since : the MPS is composed of numerous short actin filaments organized in ring-like structures transverse to the axon, and separated by various αII/βII-spectrin tetramers extended along the axon (Figure 2)
Current evidence suggests that the minimal components required for organizing the periodical lattice of the MPS are F-actin and spectrins, because pharmacological depolymerization of F-actin breaks the periodicity of spectrins, and βII-spectrin knock down affects F-actin periodic distribution (Xu et al, 2013; Zhong et al, 2014)

Summary

Introduction

Plasma membrane domain specialization is determinant for key cellular activities such as adhesion, signaling, membrane excitability, endo/exocytosis and stress resistance, among others. In 2013, a seminal study using stochastic optical reconstruction microscopy (STORM) revealed the nanoscale organization of the actin-spectrin skeleton in axons as a periodic arrangement of F-actin rings separated by ∼190 nm spectrin tetramer spacers (Xu et al, 2013), referred to as the membrane-associated periodical skeleton (MPS, Figure 2).

Results

Conclusion