Different Ca2+ affinities and functional implications of the two synaptic adhesion molecules cadherin-11 and N-cadherin.
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.
Heupel
W M
WM
University of Würzburg, Department of Anatomy and Cell Biology, D-97070 Würzburg, Germany. heupel@uni-wuerzburg.de
Baumgartner
W
W
Laymann
B
B
Drenckhahn
D
D
Golenhofen
N
N
D000199:Actins / Q000378:metabolism; D000230:Adenocarcinoma; D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D018625:Microscopy, Atomic Force; D052898:Optical Tweezers; D014162:Transfection / Q000379:methods
D000199:Actins; D015820:Cadherins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C086960:osteoblast cadherin; D002118:Calcium