IP3 receptor signaling and endothelial barrier function

Cell Mol Life Sci. 2017 Nov;74(22):4189-4207. doi: 10.1007/s00018-017-2624-8. Epub 2017 Aug 12.

Abstract

The endothelium, a monolayer of endothelial cells lining vessel walls, maintains tissue-fluid homeostasis by restricting the passage of the plasma proteins and blood cells into the interstitium. The ion Ca2+, a ubiquitous secondary messenger, initiates signal transduction events in endothelial cells that is critical to control of vascular tone and endothelial permeability. The ion Ca2+ is stored inside the intracellular organelles and released into the cytosol in response to environmental cues. The inositol 1,4,5-trisphosphate (IP3) messenger facilitates Ca2+ release through IP3 receptors which are Ca2+-selective intracellular channels located within the membrane of the endoplasmic reticulum. Binding of IP3 to the IP3Rs initiates assembly of IP3R clusters, a key event responsible for amplification of Ca2+ signals in endothelial cells. This review discusses emerging concepts related to architecture and dynamics of IP3R clusters, and their specific role in propagation of Ca2+ signals in endothelial cells.

Keywords: End-binding protein 3; Endothelial permeability; Microtubule cytoskeleton; Receptor dynamics; Signal transduction.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cytoskeleton / metabolism
  • Endothelial Cells / metabolism*
  • Humans
  • Inositol 1,4,5-Trisphosphate / chemistry
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Inositol 1,4,5-Trisphosphate Receptors / chemistry
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism*
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Kinase C-alpha / metabolism
  • Signal Transduction

Substances

  • Inositol 1,4,5-Trisphosphate Receptors
  • Protein Isoforms
  • Inositol 1,4,5-Trisphosphate
  • Protein Kinase C-alpha
  • Calcium