Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn.
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.
Lim
So-Hee
SH
Brain Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Kwon
Seok-Kyu
SK
Lee
Myung Kyu
MK
Moon
Jeonghee
J
Jeong
Dae Gwin
DG
Park
Eunha
E
Kim
Seung Jun
SJ
Park
Byung Chul
BC
Lee
Sang Chul
SC
Ryu
Seong-Eon
SE
Yu
Dae-Yeul
DY
Chung
Bong Hyun
BH
Kim
Eunjoon
E
Myung
Pyung-Keun
PK
Lee
Jae-Ran
JR
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
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