Your browser doesn't support javascript.
PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates.
Xu, Yun-Fei; Chen, Xu; Yang, Zhao; Xiao, Peng; Liu, Chun-Hua; Li, Kang-Shuai; Yang, Xiao-Zhen; Wang, Yi-Jing; Zhu, Zhong-Liang; Xu, Zhi-Gang; Zhang, Sheng; Wang, Chuan; Song, You-Chen; Zhao, Wei-Dong; Wang, Chang-He; Ji, Zhi-Liang; Zhang, Zhong-Yin; Cui, Min; Sun, Jin-Peng; Yu, Xiao.
  • Xu YF; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China.
  • Chen X; Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China.
  • Yang Z; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology, Shandong University School of Medicine, Jinan, China.
  • Xiao P; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China.
  • Liu CH; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China.
  • Li KS; Department of Physiology, Shandong First Medical University, Taian, China.
  • Yang XZ; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China.
  • Wang YJ; Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China.
  • Zhu ZL; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
  • Xu ZG; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China.
  • Zhang S; School of Life Sciences, University of Science and Technology of China, Hefei, China.
  • Wang C; Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, China.
  • Song YC; Departments of Medicinal Chemistry and Molecular Pharmacology and of Chemistry, Center for Cancer Research, and Institute for Drug Discovery, Purdue University, West Lafayette, IN, USA.
  • Zhao WD; Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
  • Wang CH; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Ji ZL; Department of Developmental Cell Biology, China Medical University, Shenyang, China.
  • Zhang ZY; Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
  • Cui M; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
  • Sun JP; Departments of Medicinal Chemistry and Molecular Pharmacology and of Chemistry, Center for Cancer Research, and Institute for Drug Discovery, Purdue University, West Lafayette, IN, USA.
  • Yu X; Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology, Shandong University School of Medicine, Jinan, China.
EMBO Rep ; 22(5): e52141, 2021 05 05.
Article in English | MEDLINE | ID: covidwho-1151026
ABSTRACT
Tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis stages has not been defined. Here we demonstrate that PTP-MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses reveal key residues that govern the interaction between PTP-MEG2 and its substrate, a peptide containing the phosphorylated NSF-pY83 site, specify PTP-MEG2 substrate selectivity, and modulate the fusion of catecholamine-containing vesicles. Unexpectedly, delineation of PTP-MEG2 mutants along with the NSF binding interface reveals that PTP-MEG2 controls the fusion pore opening through NSF independent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we uncover that PTP-MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2-pY125 and MUNC18-1-pY145 sites. Further structural and biochemical analyses confirmed the interaction of PTP-MEG2 with MUNC18-1-pY145 or DYNAMIN2-pY125 through a distinct structural basis compared with that of the NSF-pY83 site. Our studies thus provide mechanistic insights in complex exocytosis processes.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Tyrosine Phosphatases / Protein Tyrosine Phosphatases, Non-Receptor Language: English Journal: EMBO Rep Journal subject: Molecular Biology Year: 2021 Document Type: Article Affiliation country: Embr.202052141

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Tyrosine Phosphatases / Protein Tyrosine Phosphatases, Non-Receptor Language: English Journal: EMBO Rep Journal subject: Molecular Biology Year: 2021 Document Type: Article Affiliation country: Embr.202052141