Wang Fang, van Baal Jürgen, Ma Lu, Gao Xuejun, Dijkstra Jan, Bu Dengpan
State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
Animal Nutrition Group, Wageningen University and Research, Wageningen, 6708, WD, the Netherlands.
Anim Nutr. 2022 Jun 9;10:319-328. doi: 10.1016/j.aninu.2022.06.001. eCollection 2022 Sep.
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 ( > 0.89) with the mRNA and protein levels of β-casein. Similar positive correlations ( > 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.
强直性肌营养不良相关的Cdc42结合激酶α（MRCKα）是控制重要细胞过程（包括细胞骨架重组、细胞增殖和细胞存活）的信号通路的一个重要组成部分。在本研究中，我们调查了MRCKα在奶牛乳蛋白和脂肪生成中的生理作用，这需要牛乳腺上皮细胞（BMEC）中细胞骨架网络的动态和严格组织。在9头荷斯坦奶牛的样本中，我们发现乳腺中MRCKα的mRNA和蛋白表达在泌乳期间上调，并且与β-酪蛋白的mRNA和蛋白水平呈正相关（>0.89）。在用催乳素刺激24小时的BMEC原代培养物中也发现了类似的正相关（>0.79）。在这些细胞中，MRCKα的沉默降低了基础β-酪蛋白、固醇调节元件结合蛋白（SREBP）-1和细胞周期蛋白D1的蛋白水平、mTOR的磷酸化、甘油三酯分泌、细胞数量和活力，而MRCKα的过表达则产生相反的效果。值得注意的是，MRCKα的沉默完全阻止了催乳素对相同参数的刺激作用。这些数据表明，MRCKα是催乳素诱导泌乳的关键介质，通过刺激mTOR/SREBP1/细胞周期蛋白D1信号通路发挥作用。
