Abstract
Spectrin cytoskeletons are found in all metazoan cells, and their physical interactions between actin and ankyrins establish a meshwork that provides cellular structural integrity. With advanced super-resolution microscopy, the intricate spatial organization and associated functional properties of these cytoskeletons can now be analyzed with unprecedented clarity. Long neuronal processes like peripheral sensory and motor axons may be subject to intense mechanical forces including bending, stretching, and torsion. The spectrin-based cytoskeleton is essential to protect axons against these mechanical stresses. Additionally, spectrins are critical for the assembly and maintenance of axonal excitable domains including the axon initial segment and the nodes of Ranvier (NoR). These sites facilitate rapid and efficient action potential initiation and propagation in the nervous system. Recent studies revealed that pathogenic spectrin variants and diseases that protealyze and breakdown spectrins are associated with congenital neurological disorders and nervous system injury. Here, we review recent studies of spectrins in the nervous system and focus on their functions in axonal health and disease.
Highlights
Reviewed by: Juan José Garrido, Spanish National Research Council (CSIC), Spain Matthew S
Recent studies revealed that pathogenic spectrin variants and diseases that protealyze and breakdown spectrins are associated with congenital neurological disorders and nervous system injury
ΑII-spectrin is the sole α-subunit as verified at mRNA transcript (Zhang et al, 2014) and protein levels (Huang et al, 2017a). βI-spectrin is concentrated in cortical layer 2 and 4, cerebellar granule cells, and in the soma of Purkinje cells (Stankewich et al, 2010), while βII-spectrin is widely expressed in neurons and glia (Galiano et al, 2012; Zhang et al, 2013; Susuki et al, 2018). βIII-spectrin is found in the soma and dendrites of the cerebellar molecular layer
Summary
Spectrins were first isolated from the membranes of red blood cell ghosts (Marchesi and Steers, 1968) – the name spectrin derives from specter. The key molecules for membrane excitability in these regions show a similar periodicity, such as voltage-gated sodium channels (Xu et al, 2013; D’Este et al, 2017), KCNQ2 potassium channels (D’Este et al, 2017), ankyrinG (Leterrier et al, 2015), and the cell adhesion molecule neurofascin (D’Este et al, 2015; Figure 1M) These results suggest the actin-spectrin-based cytoskeleton organizes the subcellular distribution of functional units in axons. Spectrin’s periodic pattern in axons is distinct from the hexagonal network previously described in erythrocytes by EM (Byers and Branton, 1985) and STORM super-resolution microscopy (Pan et al, 2018) These remarkable differences raise several important questions including how is the architecture of spectrin-based cytoskeleton established, what are the key associated molecules involved in this process, how do these mechanisms work in a cell-type or compartment-specific manners, and what is the functional consequence of different spectrin architectures
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
