Different Ca2+ affinities and functional implications of the two synaptic adhesion molecules cadherin-11 and N-cadherin

Mol Cell Neurosci. 2008 Mar;37(3):548-58. doi: 10.1016/j.mcn.2007.12.003. Epub 2007 Dec 15.

Abstract

Cadherins of synaptic complexes are considered to be critically involved in long-term potentiation (LTP). Here we compared biophysical properties of cadherin-11 and N-cadherin, which appear to exert opposing effects on LTP, i.e., inhibition and promotion, respectively. Characterization of cadherin-11 binding by atomic force microscopy and laser tweezers revealed a significantly higher Ca(2+) affinity, with half-maximal binding (K(D)) at 0.11-0.26 mM Ca(2+), as compared to N-cadherin (K(D) approximately 0.7 mM Ca(2+)). Adhesive properties of both cadherins were modulated to a similar degree by manipulation of the actin cytoskeleton indicating to unlikely account for opposing roles in LTP induction. However, differences in Ca(2+) affinity could well explain opposing binding properties during activity-dependent transient reduction of extracellular Ca(2+) ([Ca(2+)](e)) in the synaptic cleft: whereas high frequency stimulation with drop of [Ca(2+)](e) to 0.3-0.8 mM Ca(2+) will result in significant weakening of N-cadherin adhesion, cadherin-11-based adhesion will stay mostly stable. Reduction of N-cadherin adhesion may facilitate synaptic remodeling and LTP induction, while cadherin-11 adhesion with its higher stability at low [Ca(2+)](e) may counteract this process explaining why in cadherin-11-deficient mice LTP is increased rather than decreased.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adenocarcinoma
  • Animals
  • CHO Cells
  • Cadherins / metabolism*
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Cell Line, Tumor
  • Cricetinae
  • Cricetulus
  • Gene Expression Regulation
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Mice
  • Microscopy, Atomic Force
  • Optical Tweezers
  • Transfection / methods

Substances

  • Actins
  • Cadherins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • osteoblast cadherin
  • Calcium