The role of the membrane-associated periodic skeleton in axons

The identification of the membrane periodic skeleton (MPS), composed of a periodic lattice of actin rings interconnected by spectrin tetramers, was enabled by the development of super-resolution microscopy, and brought a new exciting perspective to our view of neuronal biology. This exquisite cytoskeleton arrangement plays an important role on mechanisms regulating neuronal (dys)function. The MPS was initially thought to provide mainly for axonal mechanical stability. Since its discovery, the importance of the MPS in multiple aspects of neuronal biology has, however, emerged. These comprise its capacity to act as a signaling platform, regulate axon diameter-with important consequences on the efficiency of axonal transport and electrophysiological properties- participate in the assembly and function of the axon initial segment, and control axon microtubule stability. Recently, MPS disassembly has also surfaced as an early player in the course of axon degeneration. Here, we will discuss the current knowledge on the role of the MPS in axonal physiology and disease.

Automated summary

The identification of the membrane periodic skeleton (MPS) using super-resolution microscopy revealed a lattice of actin rings interconnected by spectrin tetramers, bringing a new perspective to neuronal biology. The exquisite cytoskeleton arrangement plays a crucial role in regulating neuronal function, beyond providing axonal mechanical stability. The MPS acts as a signaling platform, regulates axon diameter, participates in assembly and function of the axon initial segment, and controls axon microtubule stability, highlighting its importance in various aspects of neuronal biology.