한빛사논문, 상위피인용논문
- 조회5,256
Jaewon Ko1, Gilberto J. Soler-Llavina3, Marc V. Fuccillo1,3, Robert C. Malenka3, and Thomas C. Sudhof1,2
1Department of Molecular and Cellular Physiology, 2Howard Hughes Medical Institute, and 3Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305
J. Ko’s present address is Dept. of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seodaemun-gu, Seoul 120-749, South Korea.
Correspondence to Jaewon Ko; or Thomas C. Sudhof
Abstract
Neuroligins (NLs) and leucine-rich repeat transmembrane proteins (LRRTMs) are postsynaptic cell adhesion molecules that bind to presynaptic neurexins. In this paper, we show that short hairpin ribonucleic acid?mediated knockdowns (KDs) of LRRTM1, LRRTM2, and/or NL-3, alone or together as double or triple KDs (TKDs) in cultured hippocampal neurons, did not decrease synapse numbers. In neurons cultured from NL-1 knockout mice, however, TKD of LRRTMs and NL-3 induced an ∼40% loss of excitatory but not inhibitory synapses. Strikingly, synapse loss triggered by the LRRTM/NL deficiency was abrogated by chronic blockade of synaptic activity as well as by chronic inhibition of Ca2+ influx or Ca2+/calmodulin (CaM) kinases. Furthermore, postsynaptic KD of CaM prevented synapse loss in a cell-autonomous manner, an effect that was reversed by CaM rescue. Our results suggest that two neurexin ligands, LRRTMs and NLs, act redundantly to maintain excitatory synapses and that synapse elimination caused by the absence of NLs and LRRTMs is promoted by synaptic activity and mediated by a postsynaptic Ca2+/CaM-dependent signaling pathway.
논문정보
- Research article
- 2011년 07월 (BRIC 등록일 2011-07-27)
- 국외 연구진
- 생명과학 > 신경생물학
- 120회 이상 인용된 논문 (상위피인용논문 등록일 2025-01-31)
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