Antibody-directed extracellular proximity biotinylation reveals that Contactin-1 regulates axo-axonic innervation of axon initial segments

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 Aelst and Matthew N. Rasband ()
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Yuki Ogawa: Baylor College of Medicine
Brian C. Lim: Baylor College of Medicine
Shanu George: Cold Spring Harbor Laboratory
Juan A. Oses-Prieto: University of California San Francisco
Joshua M. Rasband: Baylor College of Medicine
Yael Eshed-Eisenbach: Weizmann Institute of Science
Hamdan Hamdan: Baylor College of Medicine
Supna Nair: University of California San Francisco
Francesco Boato: Cold Spring Harbor Laboratory
Elior Peles: Weizmann Institute of Science
Alma L. Burlingame: University of California San Francisco
Linda Aelst: Cold Spring Harbor Laboratory
Matthew N. Rasband: Baylor College of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Axon initial segment (AIS) cell surface proteins mediate key biological processes in neurons including action potential initiation and axo-axonic synapse formation. However, few AIS cell surface proteins have been identified. Here, we use antibody-directed proximity biotinylation to define the cell surface proteins in close proximity to the AIS cell adhesion molecule Neurofascin. To determine the distributions of the identified proteins, we use CRISPR-mediated genome editing for insertion of epitope tags in the endogenous proteins. We identify Contactin-1 (Cntn1) as an AIS cell surface protein. Cntn1 is enriched at the AIS through interactions with Neurofascin and NrCAM. We further show that Cntn1 contributes to assembly of the AIS extracellular matrix, and regulates AIS axo-axonic innervation by inhibitory basket cells in the cerebellum and inhibitory chandelier cells in the cortex.

Date: 2023
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DOI: 10.1038/s41467-023-42273-8

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