Reg1ulatory Role and Molecular Interactions of a Cell-Surface Heparan Sulfate Proteoglycan (N-syndecan) in Hippocampal Long-Term Potentiation

摘要: The cellular mechanisms responsible for synaptic plasticity involve interactions between neurons and the extracellular matrix. Heparan sulfates (HSs) constitute a group of glycosaminoglycans that accumulate in beta-amyloid deposits Alzheimer's disease influence development neuron-target contacts by interacting with other cell surface matrix molecules. However, contribution HSs to brain function is unknown. We found play crucial role long-term potentiation (LTP), finding consistent idea converging molecular are used activity-induced adults. Enzymatic cleavage HS heparitinase as well addition soluble heparin-type carbohydrates prevented expression LTP response 100 Hz/1 sec stimulation Schaffer collaterals rat hippocampal slices. A prominent carrier protein type glycans implicated regulation adult hippocampus was identified N-syndecan (syndecan-3), transmembrane proteoglycan expressed at processes CA1 pyramidal an activity-dependent manner. Addition into dendritic area tetanus-induced LTP. major substrate src-type kinases, cortactin (p80/85), tyrosine kinase fyn copurified from hippocampus. Moreover, association both rapidly increased after induction may thus act important regulator modulation neuronal connectivity transmitting signals heparin-binding factors signaling pathway.