NGL family PSD-95-interacting adhesion molecules regulate excitatory synapse formation.
Synaptic cell adhesion molecules (CAMs) regulate synapse formation through their trans-synaptic and heterophilic adhesion. Here we show that postsynaptic netrin-G ligand (NGL) CAMs associate with netrin-G CAMs in an isoform-specific manner and, through their cytosolic tail, with the abundant postsynaptic scaffold postsynaptic density-95 (PSD-95). Overexpression of NGL-2 in cultured rat neurons increased the number of PSD-95-positive dendritic protrusions. NGL-2 located on heterologous cells or beads induced functional presynaptic differentiation in contacting neurites. Direct aggregation of NGL-2 on the surface membrane of dendrites induced the clustering of excitatory postsynaptic proteins. Competitive inhibition by soluble NGL-2 reduced the number of excitatory synapses. NGL-2 knockdown reduced excitatory, but not inhibitory, synapse numbers and currents. These results suggest that NGL regulates the formation of excitatory synapses.
Kim
Seho
S
National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Burette
Alain
A
Chung
Hye Sun
HS
Kwon
Seok-Kyu
SK
Woo
Jooyeon
J
Lee
Hyun Woo
HW
Kim
Karam
K
Kim
Hyun
H
Weinberg
Richard J
RJ
Kim
Eunjoon
E
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D004622:Embryo, Mammalian; D005455:Fluorescent Antibody Technique / Q000379:methods; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D016253:Microscopy, Immunoelectron / Q000379:methods; D016296:Mutagenesis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D000075385:Netrins; D009474:Neurons / Q000166:cytology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques / Q000379:methods; D034741:RNA, Small Interfering / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology*; D013569:Synapses / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014463:Ultrasonography; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; C480698:LRRC4C protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000075385:Netrins; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D016708:Synaptophysin; D050598:Vesicular Glutamate Transport Protein 1; C073441:gephyrin; C413653:netrin-G1; D049452:Green Fluorescent Proteins