Biomaterial Database

Antibody-directed extracellular proximity biotinylation reveals Contactin-1 regulates axo-axonic innervation of axon initial segments. 2023

Yuki Ogawa, and Brian C Lim, and Shanu George, and Juan A Oses-Prieto, and Joshua M Rasband, and Yael Eshed-Eisenbach, and Supna Nair, and Francesco Boato, and Elior Peles, and Alma L Burlingame, and Linda Van Aelst, and Matthew N Rasband

Baylor College of Medicine, Department of Neuroscience, Houston, TX, USA.

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 used 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 used CRISPR-mediated genome editing for insertion of epitope tags in the endogenous proteins. We found Contactin-1 (Cntn1) among the previously unknown AIS proteins we identified. 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 is required for AIS axo-axonic innervation by inhibitory basket cells in the cerebellum and inhibitory chandelier cells in the cortex.