title: Long-term depression-inducing stimuli promote cleavage of the synaptic adhesion molecule NGL-3 through NMDA receptors, matrix metalloproteinases and presenilin/γ-secretase.
abstract: Long-term depression (LTD) reduces the functional strength of excitatory synapses through mechanisms that include the removal of AMPA glutamate receptors from the postsynaptic membrane. LTD induction is also known to result in structural changes at excitatory synapses, including the shrinkage of dendritic spines. Synaptic adhesion molecules are thought to contribute to the development, function and plasticity of neuronal synapses largely through their trans-synaptic adhesions. However, little is known about how synaptic adhesion molecules are altered during LTD. We report here that NGL-3 (netrin-G ligand-3), a postsynaptic adhesion molecule that trans-synaptically interacts with the LAR family of receptor tyrosine phosphatases and intracellularly with the postsynaptic scaffolding protein PSD-95, undergoes a proteolytic cleavage process. NGL-3 cleavage is induced by NMDA treatment in cultured neurons and low-frequency stimulation in brain slices and requires the activities of NMDA glutamate receptors, matrix metalloproteinases (MMPs) and presenilin/γ-secretase. These results suggest that NGL-3 is a novel substrate of MMPs and γ-secretase and that NGL-3 cleavage may regulate synaptic adhesion during LTD.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), , Daejeon 305-701, Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Lee
authors.forename: Eun-Jae
authors.initials: EJ
authors.lastname: Lee
authors.forename: Yoo Sung
authors.initials: YS
authors.lastname: Song
authors.forename: Eunjoon
authors.initials: E
authors.lastname: Kim
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D015151:Immunoblotting; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D053763:Presenilins / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: C549573:Lrrc4b protein, rat; D019006:Neural Cell Adhesion Molecules; D053763:Presenilins; D016194:Receptors, N-Methyl-D-Aspartate; D053829:Amyloid Precursor Protein Secretases; D020782:Matrix Metalloproteinases
keywords: NMDA receptors; long-term depression; metalloproteinase; synaptic adhesion molecules; γ-secretase