Article,

Localized Myosin II Activity Regulates Assembly and Plasticity of the Axon Initial Segment

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Neuron, 97 (3): 555--570.e6 (February 2018)
DOI: 10.1016/j.neuron.2017.12.039

Abstract

The axon initial segment (AIS) is the site of action potential generation and a locus of activity-dependent homeostatic plasticity. A multimeric complex of sodium channels, linked via a cytoskeletal scaffold of ankyrin G and beta IV spectrin to submembranous actin rings, mediates these functions. The mechanisms that specify the AIS complex to the proximal axon and underlie its plasticity remain poorly understood. Here we show phosphorylated myosin light chain (pMLC), an activator of contractile myosin II, is highly enriched in the assembling and mature AIS, where it associates with actin rings. MLC phosphorylation and myosin II contractile activity are required for AIS assembly, and they regulate the distribution of AIS components along the axon. pMLC is rapidly lost during depolarization, destabilizing actin and thereby providing a mechanism for activity-dependent structural plasticity of the AIS. Together, these results identify pMLC/myosin II activity as a common link between AIS assembly and plasticity. Berger et al. demonstrate that pMLC, a key regulator of contractile myosin II, is enriched in the axon initial segment (AIS) and is associated with actin rings. They show that pMLC and myosin II have major roles in AIS assembly and activity-dependent plasticity.

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