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Mapping axon initial segment structure and function by multiplexed proximity biotinylation

Author

Listed:
  • Hamdan Hamdan

    (Baylor College of Medicine
    Alfaisal University)

  • Brian C. Lim

    (Baylor College of Medicine)

  • Tomohiro Torii

    (Baylor College of Medicine)

  • Abhijeet Joshi

    (Baylor College of Medicine)

  • Matthias Konning

    (Baylor College of Medicine)

  • Cameron Smith

    (Baylor College of Medicine)

  • Donna J. Palmer

    (Baylor College of Medicine)

  • Philip Ng

    (Baylor College of Medicine)

  • Christophe Leterrier

    (Aix-Marseille Univ, CNRS, INP, NeuroCyto)

  • Juan A. Oses-Prieto

    (University of California San Francisco)

  • Alma L. Burlingame

    (University of California San Francisco)

  • Matthew N. Rasband

    (Baylor College of Medicine)

Abstract

Axon initial segments (AISs) generate action potentials and regulate the polarized distribution of proteins, lipids, and organelles in neurons. While the mechanisms of AIS Na+ and K+ channel clustering are understood, the molecular mechanisms that stabilize the AIS and control neuronal polarity remain obscure. Here, we use proximity biotinylation and mass spectrometry to identify the AIS proteome. We target the biotin-ligase BirA* to the AIS by generating fusion proteins of BirA* with NF186, Ndel1, and Trim46; these chimeras map the molecular organization of AIS intracellular membrane, cytosolic, and microtubule compartments. Our experiments reveal a diverse set of biotinylated proteins not previously reported at the AIS. We show many are located at the AIS, interact with known AIS proteins, and their loss disrupts AIS structure and function. Our results provide conceptual insights and a resource for AIS molecular organization, the mechanisms of AIS stability, and polarized trafficking in neurons.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13658-5
    DOI: 10.1038/s41467-019-13658-5
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    Cited by:

    1. Chun Chieh Fan & Robert Loughnan & Carolina Makowski & Diliana Pecheva & Chi-Hua Chen & Donald J. Hagler & Wesley K. Thompson & Nadine Parker & Dennis van der Meer & Oleksandr Frei & Ole A. Andreassen, 2022. "Multivariate genome-wide association study on tissue-sensitive diffusion metrics highlights pathways that shape the human brain," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. 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.
    3. Yuki Ogawa & Brian C. Lim & Shanu George & Juan A. Oses-Prieto & Joshua M. Rasband & Yael Eshed-Eisenbach & Hamdan Hamdan & Supna Nair & Francesco Boato & Elior Peles & Alma L. Burlingame & Linda Aels, 2023. "Antibody-directed extracellular proximity biotinylation reveals that Contactin-1 regulates axo-axonic innervation of axon initial segments," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. John K. Vuong & Volkan Ergin & Liang Chen & Sika Zheng, 2022. "Multilayered regulations of alternative splicing, NMD, and protein stability control temporal induction and tissue-specific expression of TRIM46 during axon formation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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