The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction

Ana Rita Costa, Sara C. Sousa, Rita Pinto-Costa, José C. Mateus, Cátia D.F. Lopes, Ana Catarina Costa, David Rosa, Diana Machado, Luis Pajuelo, Xuewei Wang, Feng Quan Zhou, António J. Pereira, Paula Sampaio, Boris Y. Rubinstein, Inês Mendes Pinto, Marko Lampe, Paulo Aguiar, Monica M. Sousa

Research output: Contribution to journalArticlepeer-review

Abstract

Neurons have a membrane periodic skeleton (MPS) composed of actin rings interconnected by spectrin. Here, combining chemical and genetic gain-and loss-of-function assays, we show that in rat hippocampal neurons the MPS is an actomyosin network that controls axonal expansion and contraction. Using super-resolution microscopy, we analyzed the localization of axonal non-muscle myosin II (NMII). We show that active NMII light chains are colocalized with actin rings and organized in a circular periodic manner throughout the axon shaft. In contrast, NMII heavy chains are mostly positioned along the longitudinal axonal axis, being able to crosslink adjacent rings. NMII filaments can play contractile or scaffolding roles determined by their position relative to actin rings and activation state. We also show that MPS destabilization through NMII inactivation affects axonal electrophysiology, increasing action potential conduction velocity. In summary, our findings open new perspectives on axon diameter regulation, with important implications in neuronal biology.

Original languageEnglish (US)
Article numbere55471
JournaleLife
Volume9
DOIs
StatePublished - Mar 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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