|SNYDER, NATHAN - Johns Hopkins University|
|CUNNINGHAM, KYLE - Johns Hopkins University|
Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/7/2019
Publication Date: 1/8/2019
Citation: Snyder, N.A., Palmer, M.V., Reinhardt, T.A., Cunningham, K.W. 2019. Milk biosynthesis requires the Golgi cation exchanger TMEM165. Journal of Biological Chemistry. 294(9):3181-3191. https://www.jbc.org/content/early/2019/01/08/jbc.RA118.006270.
Interpretive Summary: Basic mammary biology is not well understood and this lack of data limits our understanding of major dairy diseases such as mastitis. The experiment described was performed because the protein studied is a calcium/hydrogen transporter implicated in mammary calcium transport and involution. Both mammary cell calcium and and involution are critical when a cow is dried off. The process off cessation of milk production is commonly referred to as drying off with mammary involution being the scientific term. The drying off process in considered critical to a healthy mammary gland in the next lactation. So any understanding of this process is vital. We found that our protein which is a calcium/hydrogen transporter plays a small role in cell death which is a part of the drying off process. Furthermore we found that it is critical for normal lactose synthesis in lactation and therefore milk volume. While impacts are not direct to mastitis our increased understanding of mammary biology give us the tools to further advance mammary health studies.
Technical Abstract: Normal milk production by mammals is critical for normal growth and development of their offspring. Here we demonstrate that TMEM165, a Golgi-localized ion exchanger, is required for lactose synthesis in the lactating mammary gland of mice. Mutant mice lacking TMEM165 in the mammary gland produced milk that was unable to sustain normal growth rates of litters. The milk contained elevated concentrations of fat, protein, calcium, iron, and zinc. This was likely caused by decreased biosynthesis of lactose which is the major osmole in milk thus leading to a more concentrated milk. Manganese/protein ratios were significantly lower in this milk, suggesting TMEM165 supplies essential Mn2+ to lactose synthase in the Golgi complex, which may be driven by counter-transport of H+, which is a byproduct of lactose synthesis and other glycosylation reactions.