title: Release activity-dependent control of vesicle endocytosis by the synaptic adhesion molecule N-cadherin.
abstract: At synapses in the mammalian brain, continuous information transfer requires the long-term maintenance of homeostatic coupling between exo- and endocytosis of synaptic vesicles. Because classical endocytosis is orders of magnitude slower than the millisecond-range exocytosis of vesicles, high frequency vesicle fusion could potentially compromise structural stability of synapses. However, the molecular mechanisms mediating the tight coupling of exo- and endocytosis are largely unknown. Here, we investigated the role of the transsynaptic adhesion molecules N-cadherin and Neuroligin1 in regulating vesicle exo- and endocytosis by using activity-induced FM4-64 staining and by using synaptophysin-pHluorin fluorescence imaging. The synaptic adhesion molecules N-cadherin and Neuroligin1 had distinct impacts on exo- and endocytosis at mature cortical synapses. Expression of Neuroligin1 enhanced vesicle release in a N-cadherin-dependent way. Most intriguingly, expression of N-cadherin enhanced both vesicle exo- and endocytosis. Further detailed analysis of N-cadherin knockout neurons revealed that the boosting of endocytosis by N-cadherin was largely dependent on preceding high levels of vesicle release activity. In summary, regulation of vesicle endocytosis was mediated at the molecular level by N-cadherin in a release activity-dependent manner. Because of its endocytosis enhancing function, N-cadherin might play an important role in the coupling of vesicle exo- and endocytosis.
authors.affiliation: Institute of Neuro- and Sensory Physiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: van Stegen
authors.affiliation: Institute of Neuro- and Sensory Physiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors.forename: Sushma
authors.initials: S
authors.lastname: Dagar
authors.affiliation: Institute of Neuro- and Sensory Physiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Gottmann
mesh_terms: D000818:Animals; D001692:Biological Transport; D015820:Cadherins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004705:Endocytosis; D005089:Exocytosis; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D055786:Gene Knockout Techniques; D017930:Genes, Reporter; D051379:Mice; D009474:Neurons / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D015820:Cadherins; D015816:Cell Adhesion Molecules, Neuronal; C093438:neuroligin 1