Language

English

Publication Date

12-11-2023

Journal

Nature Communications

DOI

10.1038/s41467-023-44015-2

PMID

38081810

PMCID

PMC10713531

PubMedCentral® Posted Date

12-11-2023

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Axon Initial Segment, Proteome, Biotinylation, Axons, Neurons, Molecular neuroscience, Cellular neuroscience, Proteomics, Proteomics

Published Open-Access

yes

Included in

Neurosciences Commons

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