title: NGL-2 regulates input-specific synapse development in CA1 pyramidal neurons.
abstract: An important organizing feature of the CNS is that individual neurons receive input from many different sources. Independent regulation of synaptic input is critical for the function and adaptive responses of the nervous system, but the underlying molecular mechanisms are not well understood. We identify the leucine-rich repeat (LRR)-containing protein NGL-2 (Lrrc4) as a key regulator of input-specific synapse development in the hippocampus. Using genetic deletion and shRNA-mediated knockdown, we demonstrate a role for NGL-2 in regulating the strength of synaptic transmission and spine density specifically at Schaffer collateral synapses in the stratum radiatum (SR) in CA1. NGL-2 protein is restricted to SR and spine regulation requires NGL-2's LRR and PDZ-binding domains. Finally, loss of NGL-2 disrupts cooperative interactions between distal and proximal synapses in CA1 pyramidal cells. These results demonstrate that NGL-2 is critical for pathway-specific synapse development and functional integration of distinct inputs.
authors.affiliation: Neurobiology Section, Division of Biology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: DeNardo
authors.forename: Joris
authors.initials: J
authors.lastname: de Wit
authors.forename: Stefanie
authors.initials: S
authors.lastname: Otto-Hitt
authors.forename: Anirvan
authors.initials: A
authors.lastname: Ghosh
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004558:Electric Stimulation; D018274:Electroporation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D016202:N-Methylaspartate / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D000075388:Netrin-1; D009930:Organic Chemicals / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000166:cytology* / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011956:Receptors, Cell Surface / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: C417664:Alexa594; D018690:Excitatory Amino Acid Agonists; C503332:LRRC4 protein, mouse; C480698:LRRC4C protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009930:Organic Chemicals; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000075388:Netrin-1; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid