title: SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion.
abstract: Synaptic adhesion molecules regulate various aspects of synapse development, function and plasticity. These functions mainly involve trans-synaptic interactions and positive regulations, whereas cis-interactions and negative regulation are less understood. Here we report that SALM4, a member of the SALM/Lrfn family of synaptic adhesion molecules, suppresses excitatory synapse development through cis inhibition of SALM3, another SALM family protein with synaptogenic activity. Salm4-mutant (Salm4(-/-)) mice show increased excitatory synapse numbers in the hippocampus. SALM4 cis-interacts with SALM3, inhibits trans-synaptic SALM3 interaction with presynaptic LAR family receptor tyrosine phosphatases and suppresses SALM3-dependent presynaptic differentiation. Importantly, deletion of Salm3 in Salm4(-/-) mice (Salm3(-/-); Salm4(-/-)) normalizes the increased excitatory synapse number. These results suggest that SALM4 negatively regulates excitatory synapses via cis inhibition of the trans-synaptic SALM3-LAR adhesion.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute for Science and Technology, Daejeon 305-701, Korea.
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Lie
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Ji Seung
authors.initials: JS
authors.lastname: Ko
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon 305-701, Korea.
authors.forename: Su-Yeon
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon 305-701, Korea.
authors.forename: Junyeop Daniel
authors.initials: JD
authors.lastname: Roh
authors.affiliation: Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
authors.forename: Yi Sul
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Center for Cognition and Sociality, Institute for Basic Science, Daejeon 305-701, Korea.
authors.forename: Ran
authors.initials: R
authors.lastname: Noh
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon 305-701, Korea.
authors.forename: Doyoun
authors.initials: D
authors.lastname: Kim
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon 305-701, Korea.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Physiology and BK21 PLUS Project to Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Hyeyeon
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Physiology, Seoul National University School of Dentistry, Seoul 110-749, Korea.
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute for Science and Technology, Daejeon 305-701, Korea.
authors.forename: Jungyong
authors.initials: J
authors.lastname: Nam
authors.affiliation: Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Mah
authors.affiliation: Department of Anatomy and Division of Brain Korea 21, Biomedical Science, College of Medicine, Korea University, Seoul 136-705, Korea.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Lee
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute for Science and Technology, Daejeon 305-701, Korea.
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute for Science and Technology, Daejeon 305-701, Korea.
authors.forename: Ho Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Division of Brain Korea 21, Biomedical Science, College of Medicine, Korea University, Seoul 136-705, Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Physiology, Seoul National University School of Dentistry, Seoul 110-749, Korea.
authors.forename: Se-Young
authors.identifier: 0000-0001-7534-5167
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Physiology and BK21 PLUS Project to Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Um
authors.affiliation: Center for Cognition and Sociality, Institute for Basic Science, Daejeon 305-701, Korea.|Graduate School of Medical Science and Engineering, Korea Advanced Institute for Science and Technology, Daejeon 305-701, Korea.
authors.forename: Myoung-Goo
authors.initials: MG
authors.lastname: Kang
authors.affiliation: Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Bae
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Jaewon
authors.initials: J
authors.lastname: Ko
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute for Science and Technology, Daejeon 305-701, Korea.|Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon 305-701, Korea.
authors.forename: Eunjoon
authors.initials: E
authors.lastname: Kim
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C000628124:Lrfn3 protein, mouse; C000608522:Lrfn4 protein, mouse; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2