Mapping axon initial segment structure and function by multiplexed proximity biotinylation

Hamdan Hamdan, Brian C. Lim, Tomohiro Torii, Abhijeet Joshi, Matthias Konning, Cameron Smith, Donna J. Palmer, Philip Ng, Christophe Leterrier, Juan A. Oses-Prieto, Alma L. Burlingame and Matthew N. Rasband ()
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Hamdan Hamdan: Baylor College of Medicine
Brian C. Lim: Baylor College of Medicine
Tomohiro Torii: Baylor College of Medicine
Abhijeet Joshi: Baylor College of Medicine
Matthias Konning: Baylor College of Medicine
Cameron Smith: Baylor College of Medicine
Donna J. Palmer: Baylor College of Medicine
Philip Ng: Baylor College of Medicine
Christophe Leterrier: Aix-Marseille Univ, CNRS, INP, NeuroCyto
Juan A. Oses-Prieto: University of California San Francisco
Alma L. Burlingame: University of California San Francisco
Matthew N. Rasband: Baylor College of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13658-5

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DOI: 10.1038/s41467-019-13658-5

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