Leucyl-tRNA synthetase regulates lactation and cell proliferation via mTOR signaling in dairy cow mammary epithelial cells.
The role of LeuRS, an aminoacyl-tRNA synthetase, as an intracellular l-leucine sensor for the mTORC1 pathway has been the subject of much research recently. Despite this, the association between LeuRS and lactation in dairy cow mammary epithelial cells (DCMECs) remains unknown. In this study, we found that LeuRS expression in mammary gland tissue was significantly higher during lactation than pregnancy. Moreover, our data demonstrates that LeuRS is localized in the cytoplasm. Treatment with leucine increased DCMECs viability and proliferation, as well as mammalian target of rapamycin (mTOR), p-mTOR, ribosomal protein S6 kinase 1 (S6K1), p-S6K1, β-Casein, sterol regulatory element binding protein 1c (SREBP-1c), glucose transporter 1 (GLUT1), and Cyclin D1 mRNA and protein expression. Secretion of lactose and triglyceride were also increased. siRNA-mediated knockdown of LeuRS led to reduction in all of these processes. Based on these data, LeuRS up-regulates the mTOR pathway to promote proliferation and lactation of DCMECs in response to changes in the intracellular leucine concentration.
Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin 150030, China. wanglina_6688@126.com.
Lina
L
Wang
Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin 150030, China. linlu516@163.com.
Ye
Y
Lin
Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin 150030, China. bianjie.033@163.com.
Yanjie
Y
Bian
Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin 150030, China. lin211314.love@163.com.
Lili
L
Liu
Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin 150030, China. shao880330@126.com.
Li
L
Shao
Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin 150030, China. lin211314.love@163.com.
Lin
L
Lin
Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin 150030, China. qb5172@163.com.
Bo
B
Qu
Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin 150030, China. erjinzhi@126.com.
Feng
F
Zhao
Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin 150030, China. gaoxj5390@sina.com.
Xuejun
X
Gao
Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin 150030, China. qingzhangli2004@163.com.
Qingzhang
Q
Li
D000818:Animals; D002364:Caseins / Q000096:biosynthesis / Q000235:genetics; D002417:Cattle; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis / Q000235:genetics; D007774:Lactation / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism* / Q000494:pharmacology; D007935:Leucine-tRNA Ligase / Q000096:biosynthesis / Q000235:genetics*; D008321:Mammary Glands, Animal / Q000378:metabolism*; D011247:Pregnancy; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism*
D002364:Caseins; D051272:Glucose Transporter Type 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051780:Sterol Regulatory Element Binding Protein 1; D019938:Cyclin D1; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D058570:TOR Serine-Threonine Kinases; D007935:Leucine-tRNA Ligase; D007930:Leucine