OSBP-Related Protein 5L Maintains Intracellular IP3/Ca2+ Signaling and Proliferation in T Cells by Facilitating PIP2 Hydrolysis

被引：6

作者：

Xu, Mengyang ^{[1
,2
]}

Zhu, Biying ^{[1
]}

Cao, Xiuye ^{[1
]}

Li, Shannai ^{[1
]}

Li, Dan ^{[1
]}

Zhou, Huihao ^{[2
]}

Olkkonen, Vesa M. ^{[3
,4
]}

Zhong, Wenbin ^{[1
]}

Xu, Jun ^{[2
]}

Yan, Daoguang ^{[1
]}

机构：

[1] Jinan Univ, Dept Biol, Guangzhou 510632, Peoples R China

[2] Sun Yat Sen Univ, Sch Pharmaceut Sci, Res Ctr Drug Discovery, Guangzhou 510006, Peoples R China

[3] Minerva Fdn, Inst Med Res, Biomedicum 2U, Helsinki 00290, Finland

[4] Univ Helsinki, Fac Med, Dept Anat, FIN-00014 Helsinki, Finland

来源：

JOURNAL OF IMMUNOLOGY | 2020年 / 204卷 / 05期

基金：

中国国家自然科学基金; 芬兰科学院;

关键词：

PLASMA-MEMBRANE; NFAT; DIFFERENTIATION; ACTIVATION; PATHWAYS; BINDING; NETWORKS; CANCER;

D O I：

10.4049/jimmunol.1900671

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Phospholipase C (PLC) isoforms play central roles in signaling cascades by cleaving PIP2 into the second messengers IP3 and DAG. In this study, to our knowledge, we uncover that ORP5L interacts physically with PLC gamma 1 in T cells, extracts PIP2 from the plasma membrane via its ORD domain (OSBP-related domain), presents it to PLC gamma 1 (enabling IP3 generation), and eventually maintains intracellular Ca2+ homeostasis. Through this mechanism, ORP5L promotes T cell proliferation in a Ca2+-activated NFAT2-dependent manner. To our knowledge, our study uncovers a new key function of ORP5L as a critical cofactor for PLC gamma 1 catalysis and its crucial role in human T cell proliferation.

引用

页码：1134 / 1145

页数：12

共 47 条

[1] The versatility and universality of calcium signalling [J].

Berridge, MJ ;

Lipp, P ;

Bootman, MD .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2000, 1 (01) :11-21

[2] T cell receptor signalling networks: branched, diversified and bounded [J].

Brownlie, Rebecca J. ;

Zamoyska, Rose .

NATURE REVIEWS IMMUNOLOGY, 2013, 13 (04) :257-269

[3] The Amber biomolecular simulation programs [J].

Case, DA ;

Cheatham, TE ;

Darden, T ;

Gohlke, H ;

Luo, R ;

Merz, KM ;

Onufriev, A ;

Simmerling, C ;

Wang, B ;

Woods, RJ .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 2005, 26 (16) :1668-1688

[4] Cell permeable NFAT inhibitory peptide Sim-2-VIVIT inhibits T-cell activation and alleviates allergic airway inflammation and hyper-responsiveness [J].

Choi, Je-Min ;

Sohn, Jung-Ho ;

Park, Tae-Yoon ;

Park, Jung-Won ;

Lee, Sang-Kyou .

IMMUNOLOGY LETTERS, 2012, 143 (02) :170-176

[5] PI4P/phosphatidylserine countertransport at ORP5-and ORP8-mediated ER-plasma membrane contacts [J].

Chung, Jeeyun ;

Torta, Federico ;

Masai, Kaori ;

Lucast, Louise ;

Czapla, Heather ;

Tanner, Lukas B. ;

Narayanaswamy, Pradeep ;

Wenk, Markus R. ;

Nakatsu, Fubito ;

De Camilli, Pietro .

SCIENCE, 2015, 349 (6246) :428-432

[6] Phosphoinositide-specific phospholipase C in health and disease [J].

Cocco, Lucio ;

Follo, Matilde Y. ;

Manzoli, Lucia ;

Suh, Pann-Ghill .

JOURNAL OF LIPID RESEARCH, 2015, 56 (10) :1853-1860

[7] T-cell metabolism governing activation, proliferation and differentiation; a modular view [J].

Dimeloe, Sarah ;

Burgener, Anne-Valerie ;

Grahlert, Jasmin ;

Hess, Christoph .

IMMUNOLOGY, 2017, 150 (01) :35-44

[8] Oxysterol-binding protein-related protein 5 (ORP5) promotes cell proliferation by activation of mTORC1 signaling [J].

Du, Ximing ;

Zadoorian, Armella ;

Lukmantara, Ivan E. ;

Qi, Yanfei ;

Brown, Andrew J. ;

Yang, Hongyuan .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2018, 293 (10) :3806-3818

[9] A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations [J].

Duan, Y ;

Wu, C ;

Chowdhury, S ;

Lee, MC ;

Xiong, GM ;

Zhang, W ;

Yang, R ;

Cieplak, P ;

Luo, R ;

Lee, T ;

Caldwell, J ;

Wang, JM ;

Kollman, P .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 2003, 24 (16) :1999-2012

[10] Distinguishing crystallographic from biological interfaces in protein complexes: role of intermolecular contacts and energetics for classification [J].

Elez, Katarina ;

Bonvin, Alexandre M. J. J. ;

Vangone, Anna .

BMC BIOINFORMATICS, 2018, 19

← 1 2 3 4 5 →