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

Ogawa, Yuki, Lim, Brian C, George, Shanu, Oses-Prieto, Juan A, Rasband, Joshua M, Eshed-Eisenbach, Yael, Hamdan, Hamdan, Nair, Supna, Boato, Francesco, Peles, Elior, Burlingame, Alma L, Van Aelst, Linda, Rasband, Matthew N (October 2023) Antibody-directed extracellular proximity biotinylation reveals that Contactin-1 regulates axo-axonic innervation of axon initial segments. Nature Communications, 14 (1). p. 6797. ISSN 2041-1723

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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.

Item Type:	Paper
Subjects:	organs, tissues, organelles, cell types and functions > tissues types and functions > axon organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:	Van Aelst, Linda George, Shanu Boato, Francesco
Communities:	CSHL labs > Van Aelst lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	26 October 2023
Date Deposited:	01 Nov 2023 13:35
Last Modified:	10 Jan 2024 20:44
PMCID:	PMC10603070
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41288

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