title: Different pH-dependencies of the two synaptic adhesion molecules N-cadherin and cadherin-11 and the possible functional implication for long-term potentiation.
abstract: Ca(2+) -dependent adhesion molecules, cadherins, localised at synaptic sites are critically involved in long-term potentiation (LTP). N-cadherin is thought to promote LTP whereas cadherin-11 seems to counteract LTP. Since high synaptic activity is accompanied by local transient changes of the pH in the synaptic cleft, we studied whether the binding activity of cadherins is dependent on the pH and whether this might play a role during LTP. By atomic force microscopy (AFM) and laser tweezer experiments, we could show on the single molecule level as well as in a cell-based system that a decrease of the pH from 7.4 to 7.0 will result in a significant weakening of N-cadherin binding activity but in an increase of cadherin-11 binding. These differences in the pH dependencies of both molecules could be one explanation for their opposing roles during LTP. High-frequency stimulation will lead to a local acidosis in the synaptic cleft resulting in weakening of N-cadherin-mediated adhesion facilitating synaptic remodeling and LTP induction, whereas cadherin-11 bonds will be strengthened counteracting synaptic remodeling and LTP generation.
authors: Department of Cellular Neurobionic, Institute for Biology II, RWTH Aachen, Lukasstrasse 1, 52070, Aachen, Germany.
authors: Werner
authors: W
authors: Baumgartner
authors: Armin
authors: A
authors: Osmanagic
authors: Marita
authors: M
authors: Gebhard
authors: Sandra
authors: S
authors: Kraemer
authors: Nikola
authors: N
authors: Golenhofen
mesh_terms: D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017774:Long-Term Potentiation; D051379:Mice; D016716:PC12 Cells; D011485:Protein Binding; D051381:Rats; D013569:Synapses / Q000378:metabolism*
chemical_list: D015820:Cadherins; C086960:osteoblast cadherin
keywords: LTP; acidification; cell adhesion; synapse; synaptic plasticity