OSBP-Related Protein 5L Maintains Intracellular IP3/Ca2+ Signaling and Proliferation in T Cells by Facilitating PIP2 Hydrolysis
| Autor: | Vesa M. Olkkonen, Xiuye Cao, Jun Xu, Wenbin Zhong, Daoguang Yan, Shannai Li, Dan Li, Biying Zhu, Huihao Zhou, Meng-Yang Xu |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Phospholipase C Cell growth Chemistry T cell Immunology NFAT Cell biology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis Second messenger system medicine Immunology and Allergy lipids (amino acids peptides and proteins) Receptor OSBP Intracellular 030304 developmental biology |
| Zdroj: | The Journal of Immunology. 204:1134-1145 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1900671 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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