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

Neuron | 2018

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.

Pubmed ID: 29395909 RIS Download

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Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS043474
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007308

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This is a list of tools and resources that we have found mentioned in this publication.


New England Biolabs (tool)

RRID:SCR_013517

An Antibody supplier

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anti-beta IV spectrin (antibody)

RRID:AB_2315634

This polyclonal targets SD domain of beta IV spectrin

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Anti-Myelin Basic Protein (antibody)

RRID:AB_2140366

This polyclonal targets Mbp

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Anti-Kv2.1 K+ Channel Antibody (antibody)

RRID:AB_10673392

This monoclonal targets Kv2.1 K+ channel

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Anti-Pan-Neurofascin (Extracellular) Antibody (antibody)

RRID:AB_2282826

This monoclonal targets Pan-Neurofascin (extracellular)

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Anti-Ankyrin-G (Staining) Antibody (antibody)

RRID:AB_10673030

This monoclonal targets Ankyrin-G (Staining)

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Anti-Beta4-Spectrin Antibody (antibody)

RRID:AB_2315816

This monoclonal targets Beta4-spectrin

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Tau (antibody)

RRID:AB_396358

This monoclonal targets Tau

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Ankyrin G (463) (antibody)

RRID:AB_626674

This monoclonal targets Ankyrin G (463)

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Phospho-Myosin Light Chain 2 (Thr18/Ser19) Antibody (antibody)

RRID:AB_2147464

This polyclonal targets Phospho-Myosin Light Chain 2 (Thr18/Ser19)

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Ppp1r12atm1Mzhu/Ppp1r12atm1Mzhu; Tg(Acta2-cre)#Xya (organism)

RRID:MGI:5559689

Allele Detail: Targeted, Transgenic This is a legacy resource.

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C57BL/6NTac (organism)

RRID:IMSR_TAC:b6

Mus musculus with name C57BL/6NTac from IMSR.

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NTac:SD (organism)

RRID:RGD_1566440

Rattus norvegicus with name NTac:SD from RGD.

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