How calcium makes endocytic receptors attractive

Trends Biochem Sci. 2014 Feb;39(2):82-90. doi: 10.1016/j.tibs.2013.12.003. Epub 2014 Jan 4.

Abstract

Nutrients, biological waste-products, toxins, pathogens, and other ligands for endocytosis are typically captured by multidomain receptors with multiligand specificity. Upon internalization, the receptor-ligand complex segregates, followed by lysosomal degradation of the ligand and recycling of the receptor. Endosomal acidification and calcium efflux lead to the essential ligand-receptor affinity switch and separation. Recent data, including crystal structures of receptor-ligand complexes, now reveal how calcium, in different types of domain scaffolds, functions in a common way as a removable 'lynchpin' that stabilizes favorable positioning of ligand-attractive receptor residues. In addition to explaining how calcium depletion can cause ligand-receptor dissociation, the new data add further insight into how acidification contributes to dissociation through structural changes that affect the receptor calcium sites.

Keywords: C-type lectin; CUB; EGF-like; LDL receptor; scavenger receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Calcium / metabolism*
  • Calcium Signaling
  • Endocytosis / genetics*
  • Endosomes / metabolism*
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism*
  • Gene Expression Regulation
  • Humans
  • Hydrogen-Ion Concentration
  • Ligands
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*

Substances

  • Ligands
  • Receptors, Cell Surface
  • Calcium