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Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn
Author(s) -
Lim SoHee,
Kwon SeokKyu,
Lee Myung Kyu,
Moon Jeonghee,
Jeong Dae Gwin,
Park Eunha,
Kim Seung Jun,
Park Byung Chul,
Lee Sang Chul,
Ryu SeongEon,
Yu DaeYeul,
Chung Bong Hyun,
Kim Eunjoon,
Myung PyungKeun,
Lee JaeRan
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.289
Subject(s) - fyn , biology , microbiology and biotechnology , protein tyrosine phosphatase , tyrosine phosphorylation , proto oncogene tyrosine protein kinase src , cell adhesion , cell adhesion molecule , src family kinase , phosphorylation , biochemistry , cell
The receptor‐type protein tyrosine phosphatases (RPTPs) have been linked to signal transduction, cell adhesion, and neurite extension. PTPRT/RPTPρ 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.