MRCKα is a novel regulator of prolactin-induced lactogenesis in bovine mammary epithelial cells

Fang Wang; Jürgen van Baal; Lu Ma; Xuejun Gao; Jan Dijkstra; Dengpan Bu

doi:10.1016/j.aninu.2022.06.001

MRCKα is a novel regulator of prolactin-induced lactogenesis in bovine mammary epithelial cells

Anim Nutr. 2022 Jun 9:10:319-328. doi: 10.1016/j.aninu.2022.06.001. eCollection 2022 Sep.

Authors

Fang Wang^{1

2}, Jürgen van Baal², Lu Ma¹, Xuejun Gao³, Jan Dijkstra², Dengpan Bu^{1

4}

Affiliations

¹ State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
² Animal Nutrition Group, Wageningen University and Research, Wageningen, 6708, WD, the Netherlands.
³ College of Animal Science, Yangtze University, Jingzhou, 434020, China.
⁴ Joint Laboratory on Integrated Crop-Tree-Livestock Systems of the Chinese Academy of Agricultural Sciences (CAAS), Ethiopian Institute of Agricultural Research (EIAR) and World Agroforestry Center (ICRAF), Beijing, 100193, China.

Abstract

Myotonic dystrophy-related Cdc42-binding kinase alpha (MRCKα) is an integral component of signaling pathways controlling vital cellular processes, including cytoskeletal reorganization, cell proliferation and cell survival. In this study, we investigated the physiological role of MRCKα in milk protein and fat production in dairy cows, which requires a dynamic and strict organization of the cytoskeletal network in bovine mammary epithelial cells (BMEC). Within a selection of 9 Holstein cows, we found that both mRNA and protein expression of MRCKα in the mammary gland were upregulated during lactation and correlated positively (r > 0.89) with the mRNA and protein levels of β-casein. Similar positive correlations (r > 0.79) were found in a primary culture of BMEC stimulated with prolactin for 24 h. In these cells, silencing of MRCKα decreased basal β-casein, sterol-regulatory element binding protein (SREBP)-1 and cyclin D1 protein level, phosphorylation of mTOR, triglyceride secretion, cell number and viability-while overexpression of MRCKα displayed the reversed effect. Notably, silencing of MRCKα completely prevented the stimulatory action of prolactin on the same parameters. These data demonstrate that MRCKα is a critical mediator of prolactin-induced lactogenesis via stimulation of the mTOR/SREBP1/cyclin D1 signaling pathway.

Keywords: Bovine mammary gland; Cyclin D1; Mechanistic target of rapamycin; Myotonic dystrophy-related Cdc42-binding kinase alpha; Prolactin; Sterol regulatory element-binding protein-1.