Mapping axon initial segment structure and function by multiplexed proximity biotinylation - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2020

Mapping axon initial segment structure and function by multiplexed proximity biotinylation

Résumé

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.

Domaines

Neurobiologie
Fichier principal
Vignette du fichier
s41467-019-13658-5.pdf (6.8 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

hal-02427822 , version 1 (04-01-2020)

Licence

Paternité

Identifiants

Citer

Hamdan Hamdan, Brian C Lim, Tomohiro Torii, Abhijeet Joshi, Matthias Konning, et al.. Mapping axon initial segment structure and function by multiplexed proximity biotinylation. Nature Communications, 2020, 11 (1), ⟨10.1038/s41467-019-13658-5⟩. ⟨hal-02427822⟩
119 Consultations
109 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More