Direct visualization of single-molecule membrane protein interactions in living cells

PLoS Biol. 2018 Dec 13;16(12):e2006660. doi: 10.1371/journal.pbio.2006660. eCollection 2018 Dec.

Abstract

Interactions between membrane proteins are poorly understood despite their importance in cell signaling and drug development. Here, we present a co-immunoimmobilization assay (Co-II) enabling the direct observation of membrane protein interactions in single living cells that overcomes the limitations of currently prevalent proximity-based indirect methods. Using Co-II, we investigated the transient homodimerizations of epidermal growth factor receptor (EGFR) and beta-2 adrenergic receptor (β2-AR) in living cells, revealing the differential regulation of these receptors' dimerizations by molecular conformations and microenvironment in a plasma membrane. Co-II should provide a simple, rapid, and robust platform for visualizing both weak and strong protein interactions in the plasma membrane of living cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Membrane / metabolism
  • ErbB Receptors / physiology
  • Humans
  • Immunoprecipitation / methods*
  • Membrane Proteins / physiology
  • Protein Binding / physiology
  • Protein Interaction Mapping / methods*
  • Receptors, Adrenergic, beta-2 / physiology
  • Signal Transduction
  • Single-Cell Analysis / methods*

Substances

  • Membrane Proteins
  • Receptors, Adrenergic, beta-2
  • ErbB Receptors

Grants and funding

National Research Foundation of Korea (grant number NRF-2016K1A1A2912722). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. National Research Foundation of Korea (grant number NRF-2016R1A6A3A11935984). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Samsung Science and Technology Foundation (grant number SSTF-BA1402-11). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.