Otani Kei, Niwa Yuki, Suzuki Takehiro, Sato Natsumi, Sasazawa Yukiko, Dohmae Naoshi, Simizu Siro
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Japan.
Biochem Biophys Res Commun. 2018 Apr 6;498(3):466-472. doi: 10.1016/j.bbrc.2018.02.210. Epub 2018 Mar 1.
Granulocyte colony-stimulating factor (G-CSF) receptor (G-CSFR) is a type I cytokine receptor which is involved in hematopoietic cell maturation. G-CSFR has three putative C-mannosylation sites at W253, W318, and W446; however, it is not elucidated whether G-CSFR is C-mannosylated or not. In this study, we first demonstrated that G-CSFR was C-mannosylated at only W318. We also revealed that C-mannosylation of G-CSFR affects G-CSF-dependent downstream signaling through changing ligand binding capability but not cell surface localization. Moreover, C-mannosylation of G-CSFR was functional and regulated granulocytic differentiation in myeloid 32D cells. In conclusion, we found that G-CSFR is C-mannosylated at W318 and that this C-mannosylation has role(s) for myeloid cell differentiation through regulating downstream signaling.
粒细胞集落刺激因子（G-CSF）受体（G-CSFR）是一种I型细胞因子受体，参与造血细胞的成熟过程。G-CSFR在W253、W318和W446处有三个假定的C-甘露糖基化位点；然而，G-CSFR是否进行了C-甘露糖基化尚未阐明。在本研究中，我们首先证明G-CSFR仅在W318处发生C-甘露糖基化。我们还发现，G-CSFR的C-甘露糖基化通过改变配体结合能力而非细胞表面定位来影响G-CSF依赖的下游信号传导。此外，G-CSFR的C-甘露糖基化具有功能，并调节髓系32D细胞中的粒细胞分化。总之，我们发现G-CSFR在W318处发生C-甘露糖基化，并且这种C-甘露糖基化通过调节下游信号传导对髓系细胞分化具有作用。
