title: Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn.
abstract: The receptor-type protein tyrosine phosphatases (RPTPs) have been linked to signal transduction, cell adhesion, and neurite extension. PTPRT/RPTPrho is exclusively expressed in the central nervous system and regulates synapse formation by interacting with cell adhesion molecules and Fyn protein tyrosine kinase. Overexpression of PTPRT in cultured neurons increased the number of excitatory and inhibitory synapses by recruiting neuroligins that interact with PTPRT through their ecto-domains. In contrast, knockdown of PTPRT inhibited synapse formation and withered dendrites. Incubation of cultured neurons with recombinant proteins containing the extracellular region of PTPRT reduced the number of synapses by inhibiting the interaction between ecto-domains. Synapse formation by PTPRT was inhibited by phosphorylation of tyrosine 912 within the membrane-proximal catalytic domain of PTPRT by Fyn. This tyrosine phosphorylation reduced phosphatase activity of PTPRT and reinforced homophilic interactions of PTPRT, thereby preventing the heterophilic interaction between PTPRT and neuroligins. These results suggest that brain-specific PTPRT regulates synapse formation through interaction with cell adhesion molecules, and this function and the phosphatase activity are attenuated through tyrosine phosphorylation by the synaptic tyrosine kinase Fyn.
authors.affiliation: Brain Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: So-Hee
authors.initials: SH
authors.lastname: Lim
authors.forename: Seok-Kyu
authors.initials: SK
authors.lastname: Kwon
authors.forename: Myung Kyu
authors.initials: MK
authors.lastname: Lee
authors.forename: Jeonghee
authors.initials: J
authors.lastname: Moon
authors.forename: Dae Gwin
authors.initials: DG
authors.lastname: Jeong
authors.forename: Eunha
authors.initials: E
authors.lastname: Park
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kim
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Park
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Lee
authors.forename: Seong-Eon
authors.initials: SE
authors.lastname: Ryu
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
authors.forename: Bong Hyun
authors.initials: BH
authors.lastname: Chung
authors.forename: Eunjoon
authors.initials: E
authors.lastname: Kim
authors.forename: Pyung-Keun
authors.initials: PK
authors.lastname: Myung
authors.forename: Jae-Ran
authors.initials: JR
authors.lastname: Lee
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules; D034741:RNA, Small Interfering; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; C516865:PTPRT protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2