A subtype-specific function for the extracellular domain of neuroligin 1 in hippocampal LTP.
At neuronal excitatory synapses, two major subtypes of the synaptic adhesion molecule neuroligin are present. These subtypes, neuroligin 1 and neuroligin 3, have roles in synaptogenesis and synaptic maintenance that appear largely overlapping. In this study, we combine electrophysiology with molecular deletion and replacement of these proteins to identify similarities and differences between these subtypes. In doing so, we identify a subtype-specific role in LTP for neuroligin 1 in young CA1, which persists into adulthood in the dentate gyrus. As neuroligin 3 showed no requirement for LTP, we constructed chimeric proteins of the two excitatory neuroligin subtypes to identify the molecular determinants particular to the unique function of neuroligin 1. Using in vivo molecular replacement experiments, we find that these unique functions depend on a region in its extracellular domain containing the B site splice insertion previously shown to determine specificity of neurexin binding.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
Seth L
SL
Shipman
Roger A
RA
Nicoll
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002461:Cell Line, Transformed; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D018709:Statistics, Nonparametric; D013238:Stereotaxic Techniques; D014161:Transduction, Genetic; D014162:Transfection; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D015816:Cell Adhesion Molecules, Neuronal; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D008565:Membrane Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D011810:Quinoxalines; C093438:neuroligin 1; C098004:neuroligin 3; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid