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Immunoproximity biotinylation reveals the axon initial segment proteome

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  • Wei Zhang

    (Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University
    PKU-Tsinghua Center for Life Science, Peking University
    Baylor College of Medicine)

  • Yu Fu

    (Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University)

  • Luxin Peng

    (Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University)

  • Yuki Ogawa

    (Baylor College of Medicine)

  • Xiaoyun Ding

    (Baylor College of Medicine)

  • Anne Rasband

    (Baylor College of Medicine)

  • Xinyue Zhou

    (PKU-Tsinghua Center for Life Science, Peking University)

  • Maya Shelly

    (Stony Brook University)

  • Matthew N. Rasband

    (Baylor College of Medicine)

  • Peng Zou

    (Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University
    PKU-Tsinghua Center for Life Science, Peking University
    Peking University
    Chinese Institute for Brain Research (CIBR))

Abstract

The axon initial segment (AIS) is a specialized neuronal compartment required for action potential generation and neuronal polarity. However, understanding the mechanisms regulating AIS structure and function has been hindered by an incomplete knowledge of its molecular composition. Here, using immuno-proximity biotinylation we further define the AIS proteome and its dynamic changes during neuronal maturation. Among the many AIS proteins identified, we show that SCRIB is highly enriched in the AIS both in vitro and in vivo, and exhibits a periodic architecture like the axonal spectrin-based cytoskeleton. We find that ankyrinG interacts with and recruits SCRIB to the AIS. However, loss of SCRIB has no effect on ankyrinG. This powerful and flexible approach further defines the AIS proteome and provides a rich resource to elucidate the mechanisms regulating AIS structure and function.

Suggested Citation

  • Wei Zhang & Yu Fu & Luxin Peng & Yuki Ogawa & Xiaoyun Ding & Anne Rasband & Xinyue Zhou & Maya Shelly & Matthew N. Rasband & Peng Zou, 2023. "Immunoproximity biotinylation reveals the axon initial segment proteome," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44015-2
    DOI: 10.1038/s41467-023-44015-2
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    References listed on IDEAS

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    1. Matthew S. Grubb & Juan Burrone, 2010. "Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability," Nature, Nature, vol. 465(7301), pages 1070-1074, June.
    2. Kelsie Eichel & Takeshi Uenaka & Vivek Belapurkar & Rui Lu & Shouqiang Cheng & Joseph S. Pak & Caitlin A. Taylor & Thomas C. Südhof & Robert Malenka & Marius Wernig & Engin Özkan & David Perrais & Kan, 2022. "Endocytosis in the axon initial segment maintains neuronal polarity," Nature, Nature, vol. 609(7925), pages 128-135, September.
    3. Hamdan Hamdan & Brian C. Lim & Tomohiro Torii & Abhijeet Joshi & Matthias Konning & Cameron Smith & Donna J. Palmer & Philip Ng & Christophe Leterrier & Juan A. Oses-Prieto & Alma L. Burlingame & Matt, 2020. "Mapping axon initial segment structure and function by multiplexed proximity biotinylation," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    4. Bettina Winckler & Paul Forscher & Ira Mellman, 1999. "A diffusion barrier maintains distribution of membrane proteins in polarized neurons," Nature, Nature, vol. 397(6721), pages 698-701, February.
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