Autophagosome content profiling using proximity biotinylation proteomics coupled to protease digestion in mammalian cells

STAR Protoc. 2021 Apr 27;2(2):100506. doi: 10.1016/j.xpro.2021.100506. eCollection 2021 Jun 18.

Abstract

The ascorbate peroxidase APEX2 is commonly used to study the neighborhood of a protein of interest by proximity-dependent biotinylation. Here, we describe a protocol for sample processing compatible with immunoblotting and mass spectrometry, suitable to specifically map the content of autophagosomes and potentially other short-lived endomembrane transport vesicles without the need of subcellular fractionation. By combining live-cell biotinylation with proteinase K digestion of cell homogenates, proteins enriched in membrane-protected compartments can be readily enriched and identified. For complete details on the use and execution of this protocol, please refer to Zellner et al. (2021).

Keywords: Cell Biology; Mass Spectrometry; Molecular Biology; Protein Biochemistry; Proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagosomes* / chemistry
  • Autophagosomes* / metabolism
  • Biotinylation
  • DNA-(Apurinic or Apyrimidinic Site) Lyase* / chemistry
  • DNA-(Apurinic or Apyrimidinic Site) Lyase* / metabolism
  • Endonucleases* / chemistry
  • Endonucleases* / metabolism
  • Endopeptidase K / chemistry*
  • HeLa Cells
  • Humans
  • Multifunctional Enzymes* / chemistry
  • Multifunctional Enzymes* / metabolism
  • Proteolysis*
  • Proteomics*

Substances

  • Multifunctional Enzymes
  • Endonucleases
  • Endopeptidase K
  • APEX2 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase