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OSBP-Related Protein 5L Maintains Intracellular IP3/Ca2+ Signaling and Proliferation in T Cells by Facilitating PIP2 Hydrolysis.
Xu, Mengyang; Zhu, Biying; Cao, Xiuye; Li, Shannai; Li, Dan; Zhou, Huihao; Olkkonen, Vesa M; Zhong, Wenbin; Xu, Jun; Yan, Daoguang.
Afiliação
  • Xu M; Department of Biology, Jinan University, Guangzhou 510632, China.
  • Zhu B; Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
  • Cao X; Department of Biology, Jinan University, Guangzhou 510632, China.
  • Li S; Department of Biology, Jinan University, Guangzhou 510632, China.
  • Li D; Department of Biology, Jinan University, Guangzhou 510632, China.
  • Zhou H; Department of Biology, Jinan University, Guangzhou 510632, China.
  • Olkkonen VM; Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
  • Zhong W; Minerva Foundation Institute for Medical Research, Biomedicum 2U, Helsinki 00290, Finland; and.
  • Xu J; Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki 00014, Finland.
  • Yan D; Department of Biology, Jinan University, Guangzhou 510632, China; tzhongwb@jnu.edu.cn tydg@jnu.edu.cn junxu@biochemomes.com.
J Immunol ; 204(5): 1134-1145, 2020 03 01.
Article em En | MEDLINE | ID: mdl-31953353
ABSTRACT
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 PLCγ1 in T cells, extracts PIP2 from the plasma membrane via its ORD domain (OSBP-related domain), presents it to PLCγ1 (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 PLCγ1 catalysis and its crucial role in human T cell proliferation.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Esteroides / Inositol 1,4,5-Trifosfato / Fosfatidilinositol 4,5-Difosfato / Sinalização do Cálcio / Proliferação de Células Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Esteroides / Inositol 1,4,5-Trifosfato / Fosfatidilinositol 4,5-Difosfato / Sinalização do Cálcio / Proliferação de Células Idioma: En Ano de publicação: 2020 Tipo de documento: Article