Actin dynamics in the growth cone: a key player in axon regeneration.

Neuronal development, maintenance and function depends on the tight regulation of cytoskeleton organization and dynamics. Following injury, adult central nervous system neurons have a limited ability to regenerate and to recapitulate their robust developmental axon growth. This decreased regenerative capacity is set by their inability to establish regeneration-competent growth cones. Growth cones are actin-enriched structures that regulate axon extension rate and direction. During neuronal development, increasing actin dynamics in the growth cone through the regulation of the activity of specific actin-binding proteins leads to increased axon elongation. Here, we will focus on recent findings showing that enhanced axon regeneration in the adult nervous system can be achieved by promoting actin dynamics, or by decreasing actomyosin contraction in the growth cone. These discoveries underscore the importance of actin organization in the growth cone as a key factor to promote axon (re)growth that should be further explored in the future.

The neuronal and actin commitment: Why do neurons need rings?

The role of the actin cytoskeleton in neurons has been extensively studied in actin-enriched compartments such as the growth cone and dendritic spines. The recent discovery of actin rings in the axon shaft and in dendrites, together with the identification of axon actin trails, has advanced our understanding on actin organization and dynamics in neurons. However, specifically in the case of actin rings, the mechanisms regulating their nucleation and assembly, and the functions that they may exert in axons and dendrites remain largely unexplored. Here we discuss the possible structural, mechanistic and functional properties of the subcortical neuronal cytoskeleton putting the current knowledge in perspective with the information available on actin rings formed in other biological contexts, and with the organization of actin-spectrin lattices in other cell types. The detailed analysis of these novel neuronal actin ring structures, together with the elucidation of the function of actin-binding proteins in neuron biology, has a large potential to uncover new mechanisms of neuronal function under normal conditions that may have impact in our understanding of axon degeneration and regeneration. © 2016 Wiley Periodicals, Inc.

The Actin-Binding Protein α-Adducin Is Required for Maintaining Axon Diameter.

The actin-binding protein adducin was recently identified as a component of the neuronal subcortical cytoskeleton. Here, we analyzed mice lacking adducin to uncover the function of this protein in actin rings. α-adducin knockout mice presented progressive axon enlargement in the spinal cord and optic and sciatic nerves, followed by axon degeneration and loss. Using stimulated emission depletion super-resolution microscopy, we show that a periodic subcortical actin cytoskeleton is assembled in every neuron type inspected including retinal ganglion cells and dorsal root ganglia neurons. In neurons devoid of adducin, the actin ring diameter increased, although the inter-ring periodicity was maintained. In vitro, the actin ring diameter adjusted as axons grew, suggesting the lattice is dynamic. Our data support a model in which adducin activity is not essential for actin ring assembly and periodicity but is necessary to control the diameter of both actin rings and axons and actin filament growth within rings.