GFP-Aequorin Protein Sensor for Ex Vivo and In Vivo Imaging of Ca(2+) Dynamics in High-Ca(2+) Organelles

Cell Chem Biol. 2016 Jun 23;23(6):738-45. doi: 10.1016/j.chembiol.2016.05.010. Epub 2016 Jun 9.

Abstract

Proper functioning of organelles such as the ER or the Golgi apparatus requires luminal accumulation of Ca(2+) at high concentrations. Here we describe a ratiometric low-affinity Ca(2+) sensor of the GFP-aequorin protein (GAP) family optimized for measurements in high-Ca(2+) concentration environments. Transgenic animals expressing the ER-targeted sensor allowed monitoring of Ca(2+) signals inside the organelle. The use of the sensor was demonstrated under three experimental paradigms: (1) ER Ca(2+) oscillations in cultured astrocytes, (2) ex vivo functional mapping of cholinergic receptors triggering ER Ca(2+) release in acute hippocampal slices from transgenic mice, and (3) in vivo sarcoplasmic reticulum Ca(2+) dynamics in the muscle of transgenic flies. Our results provide proof of the suitability of the new biosensors to monitor Ca(2+) dynamics inside intracellular organelles under physiological conditions and open an avenue to explore complex Ca(2+) signaling in animal models of health and disease.

Keywords: GECI; GFP; Golgi apparatus; aequorin; biosensor; calcium; endoplasmic reticulum; organelles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aequorin / analysis*
  • Aequorin / chemistry
  • Aequorin / genetics
  • Aequorin / metabolism
  • Animals
  • Calcium / analysis*
  • Calcium / metabolism*
  • Drosophila melanogaster
  • Endoplasmic Reticulum / chemistry
  • Endoplasmic Reticulum / metabolism
  • Green Fluorescent Proteins / analysis*
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Imaging
  • Organelles / chemistry
  • Organelles / metabolism*

Substances

  • Green Fluorescent Proteins
  • Aequorin
  • Calcium