FAM19A1 is a new ligand for GPR1 that modulates neural stem-cell proliferation and differentiation
Zheng, Can1,2; Chen, Dixin1,2; Zhang, Yan1,2; Bai, Yun3; Huang, Shiyang1,2; Zheng, Danfeng1,2; Liang, Weiwei1,2; She, Shaoping1,2; Peng, Xinjian1,2; Wang, Pingzhang1,2,4; Mo, Xiaoning4; Song, Quansheng1,2,4; Lv, Ping1,2,4; Huang, Jing1,2,4; Ye, Richard D.5; Wang, Ying1,2,4
Source PublicationFASEB JOURNAL
AbstractFAM19A1 is a member of the family with sequence similarity 19 with unknown function. FAM19A1 mRNA expression is restricted to the CNS. Here, we report that FAM19A1 is a classic secretory protein, and expression levels correlate with brain development, increasing from embryonic d 12.5, peaking between postnatal d (P)1 and P7 and decreasing at wk 8. The adult hippocampus is a region of FAM19A1 high expression. Recombinant FAM19A1 suppressed the proliferation and self-renewal of neural stem cells (NSCs) and altered the lineage progression of NSCs with promoted neuron differentiation and suppressed astrocyte differentiation. Although GPCR 1 (GPR1) has been reported to be expressed in the CNS, its functions in the brain remain unclear. We identified GPR1 to be a functional receptor for FAM19A1. FAM19A1 interacted with GPR1 via the N-terminal domain (GPR1-ND), and its NSC modulatory functions required the Rho-associated protein kinase (ROCK) /ERK1/2 and ROCK/signal transducer and activator of transcription 3 signaling pathways. GPR1-ND that selectively bound to FAM19A1 neutralized the effects of FAM19A1 on NSC functions. Taken together, our results show, for the first time to our knowledge, that FAM19A1 is a novel regulatory factor of the proliferation and differentiation of NSCs, and identified a novel mechanism by which GPCR mediates the effects of FAM19A1 on NSC functions that may be important for brain development and neurogenesis. Additional exploration of the functions of FAM19A1 and GPR1 in the CNS may broaden the range of therapeutic options available for major brain disorders.Zheng, C., Chen, D., Zhang, Y., Bai, Y., Huang, S., Zheng, D., Liang, W., She, S., Peng, X., Wang, P., Mo, X., Song, Q., Lv, P., Huang, J., Ye, R. D., Wang, Y. FAM19A1 is a new ligand for GPR1 that modulates neural stem-cell proliferation and differentiation.
Keywordneural stem cell GPCR cytokines
URLView the original
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Biology ; Cell Biology
WOS IDWOS:000447172000010
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Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Peking Univ, Dept Immunol, Sch Basic Med Sci, Hlth Sci Ctr, 38 Xueyuan Rd, Beijing 100191, Peoples R China;
2.Peking Univ, Key Lab Med Immunol, Minist Hlth, Hlth Sci Ctr, Beijing, Peoples R China;
3.Peking Univ, Hlth Sci Ctr, Dept Cell Biol, Sch Basic Med Sci, Beijing, Peoples R China;
4.Peking Univ, Ctr Human Dis Genom, Beijing, Peoples R China;
5.Univ Macau, Inst Chinese Med Sci, Taipa 999078, Macau, Peoples R China
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Zheng, Can,Chen, Dixin,Zhang, Yan,et al. FAM19A1 is a new ligand for GPR1 that modulates neural stem-cell proliferation and differentiation[J]. FASEB JOURNAL,2018,32(11):5874-5890.
APA Zheng, Can.,Chen, Dixin.,Zhang, Yan.,Bai, Yun.,Huang, Shiyang.,...&Wang, Ying.(2018).FAM19A1 is a new ligand for GPR1 that modulates neural stem-cell proliferation and differentiation.FASEB JOURNAL,32(11),5874-5890.
MLA Zheng, Can,et al."FAM19A1 is a new ligand for GPR1 that modulates neural stem-cell proliferation and differentiation".FASEB JOURNAL 32.11(2018):5874-5890.
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