FRET between cardiac Na+ channel subunits measured with a confocal microscope and a streak camera

Nat Biotechnol. 2004 Feb;22(2):220-4. doi: 10.1038/nbt935. Epub 2004 Jan 18.

Abstract

When and where proteins associate is a central question in many biomolecular studies. Förster resonance energy transfer (FRET) measurements can be used to address this question when the interacting proteins are labeled with appropriate donor and acceptor fluorophores. We describe an improved method to determine FRET efficiency that uses a mode-locked laser, a confocal microscope and a streak camera. We applied this method to study the association of alpha and beta(1) subunits of the human cardiac sodium channel. The subunits were tagged with the cyan and yellow variants of the green fluorescent protein (GFP) and expressed in human embryonic kidney (HEK293) cells. Pronounced FRET between the channel subunits in the endoplasmic reticulum (ER) suggested that the subunits associate before they reach the plasma membrane. The described method allows simultaneous measurement of donor and acceptor fluorescence decays and provides an intrinsically validated estimate of FRET efficiency.

Publication types

  • Evaluation Study
  • Letter

MeSH terms

  • Cell Line
  • Fluorescence Resonance Energy Transfer / methods*
  • Humans
  • Kidney / cytology
  • Kidney / embryology
  • Kidney / metabolism*
  • Microscopy, Confocal / methods*
  • Microscopy, Video / methods*
  • Muscle Proteins / metabolism*
  • Muscle Proteins / ultrastructure
  • NAV1.5 Voltage-Gated Sodium Channel
  • Protein Structure, Tertiary
  • Sodium Channels / metabolism*
  • Sodium Channels / ultrastructure

Substances

  • Muscle Proteins
  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Sodium Channels