Actin is an integral part of the neuronal cytoskeleton as it is involved in the regulation of neuronal polarization, cell morphology, the development of neuronal processes (i.e., growth cones with lamellipodial and filopodial extensions and dendritic spines), intracellular trafficking, and synaptic plasticity (dynamic changes in dendritic spine number and/or morphology)1-3. Actin’s presence in growth cones and dendritic spines have garnered the attention of scientists for decades; however, actin is also found in neuronal axons, though its presence there has been described as the “black sheep of the neuronal actin family”4. This is because the exact details of actin’s structure and role in the axon are unknown. Recently, significant advances have been made in unraveling the structure of axonal actin with the discovery of the periodic membrane skeleton (PMS) by nanoscopic microscopy5 (Fig. 1). This newsletter discusses the discovery, structure, and possible functions of the PMS in axons.
Discovered in 2013, the PMS is a type of cortical actin and the primary component of the actin cortex, a mixture of F-actin and actin binding proteins which supports eukaryotic cells’ plasma membrane and membrane-associated processes such as endo- and exocytosis and cell motility4,5. In neuronal axons, including the initial segment6, the PMS consists of short actin filaments bundled into evenly spaced rings that wrap around the circumference of the axon with a periodicity of 180-190 nanometers5-9 (Fig. 1). The short filaments are stabilized by an adducin cap which controls the diameter of actin rings and axons, as well as actin filament growth within the rings6,10. Adjacent actin rings are secured through cross-linkage by spectrin tetramers (bII in the axon proper and bIV in the axon initial segment)6,8,11.