title: SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development.
abstract: Synaptogenic adhesion molecules play critical roles in synapse formation. SALM5/Lrfn5, a SALM/Lrfn family adhesion molecule implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons, but its presynaptic ligand remains unknown. We found that SALM5 interacts with the Ig domains of LAR family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPδ, and PTPσ). These interactions are strongly inhibited by the splice insert B in the Ig domain region of LAR-RPTPs, and mediate SALM5-dependent presynaptic differentiation in contacting axons. In addition, SALM5 regulates AMPA receptor-mediated synaptic transmission through mechanisms involving the interaction of postsynaptic SALM5 with presynaptic LAR-RPTPs. These results suggest that postsynaptic SALM5 promotes synapse development by trans-synaptically interacting with presynaptic LAR-RPTPs and is important for the regulation of excitatory synaptic strength.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Yeonsoo
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Jungyong
authors.initials: J
authors.lastname: Nam
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, Faculty of Health Sciences, University of Bristol, Whitson Street, Bristol BS1 3NY, United Kingdom.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Whitcomb
authors.affiliation: Department of Nuclear Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, 463-707, Korea.
authors.forename: Yoo Sung
authors.initials: YS
authors.lastname: Song
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon 305-701, Korea.
authors.forename: Doyoun
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Jeon
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.|Department of Physiology and BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Um
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Jooyeon
authors.initials: J
authors.lastname: Woo
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Seok-Kyu
authors.initials: SK
authors.lastname: Kwon
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon 305-701, Korea.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Mah
authors.affiliation: Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea.
authors.forename: Ho Min
authors.initials: HM
authors.lastname: Kim
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: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, Faculty of Health Sciences, University of Bristol, Whitson Street, Bristol BS1 3NY, United Kingdom.|Centre for Synaptic Plasticity, University of Bristol, Bristol BS1 3NY, United Kingdom.
authors.forename: Kwangwook
authors.initials: K
authors.lastname: Cho
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon 305-701, Korea.|Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon 305-701, Korea.
authors.forename: Eunjoon
authors.initials: E
authors.lastname: Kim
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C000612989:SALM5 protein, mouse; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2