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Proteomic and functional analyses of the periodic membrane skeleton in neurons

Author

Listed:
  • Ruobo Zhou

    (Harvard University
    Harvard University
    Harvard University
    The Pennsylvania State University)

  • Boran Han

    (Harvard University
    Harvard University
    Harvard University)

  • Roberta Nowak

    (The Scripps Research Institute)

  • Yunzhe Lu

    (Tufts University School of Medicine)

  • Evan Heller

    (Harvard University
    Harvard University
    Harvard University)

  • Chenglong Xia

    (Harvard University
    Harvard University
    Harvard University)

  • Athar H. Chishti

    (Tufts University School of Medicine)

  • Velia M. Fowler

    (The Scripps Research Institute
    The University of Delaware)

  • Xiaowei Zhuang

    (Harvard University
    Harvard University
    Harvard University)

Abstract

Actin, spectrin, and associated molecules form a membrane-associated periodic skeleton (MPS) in neurons. The molecular composition and functions of the MPS remain incompletely understood. Here, using co-immunoprecipitation and mass spectrometry, we identified hundreds of potential candidate MPS-interacting proteins that span diverse functional categories. We examined representative proteins in several of these categories using super-resolution imaging, including previously unknown MPS structural components, as well as motor proteins, cell adhesion molecules, ion channels, and signaling proteins, and observed periodic distributions characteristic of the MPS along the neurites for ~20 proteins. Genetic perturbations of the MPS and its interacting proteins further suggested functional roles of the MPS in axon-axon and axon-dendrite interactions and in axon diameter regulation, and implicated the involvement of MPS interactions with cell adhesion molecules and non-muscle myosin in these roles. These results provide insights into the interactome of the MPS and suggest previously unknown functions of the MPS in neurons.

Suggested Citation

  • Ruobo Zhou & Boran Han & Roberta Nowak & Yunzhe Lu & Evan Heller & Chenglong Xia & Athar H. Chishti & Velia M. Fowler & Xiaowei Zhuang, 2022. "Proteomic and functional analyses of the periodic membrane skeleton in neurons," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30720-x
    DOI: 10.1038/s41467-022-30720-x
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    References listed on IDEAS

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    1. Stéphane Vassilopoulos & Solène Gibaud & Angélique Jimenez & Ghislaine Caillol & Christophe Leterrier, 2019. "Ultrastructure of the axonal periodic scaffold reveals a braid-like organization of actin rings," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
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    Cited by:

    1. Andrea Ghisleni & Mayte Bonilla-Quintana & Michele Crestani & Zeno Lavagnino & Camilla Galli & Padmini Rangamani & Nils C. Gauthier, 2024. "Mechanically induced topological transition of spectrin regulates its distribution in the mammalian cell cortex," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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