Milk biosynthesis requires the Golgi cation exchanger TMEM165
| Autor: | Nathan A. Snyder, Mitchell V. Palmer, Kyle W. Cunningham, Timothy A. Reinhardt |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Osmosis Golgi Apparatus chemistry.chemical_element Calcium Biochemistry Antiporters Gene Knockout Techniques Mice 03 medical and health sciences chemistry.chemical_compound symbols.namesake Mammary Glands Animal Biosynthesis Animals Lactation Lactose Cation Transport Proteins Molecular Biology 030102 biochemistry & molecular biology biology Body Weight Lactose synthase Cell Biology Golgi apparatus Transmembrane protein Milk 030104 developmental biology chemistry biology.protein symbols Female Immunostaining Homeostasis |
| Zdroj: | Journal of Biological Chemistry. 294:3181-3191 |
| ISSN: | 0021-9258 |
| Popis: | Milk is a hallmark of mammals that is critical for normal growth and development of offspring. During biosynthesis of lactose in the Golgi complex, H(+) is produced as a by-product, and there is no known mechanism for maintaining luminal pH within the physiological range. Here, using conditional, tissue-specific knockout mice, immunostaining, and biochemical assays, we test whether the putative H(+)/Ca(2+)/Mn(2+) exchanger known as TMEM165 (transmembrane protein 165) participates in normal milk production. We find TMEM165 is crucial in the lactating mammary gland for normal biosynthesis of lactose and for normal growth rates of nursing pups. The milk of TMEM165-deficient mice contained elevated concentrations of fat, protein, iron, and zinc, which are likely caused by decreased osmosis-mediated dilution of the milk caused by the decreased biosynthesis of lactose. When normalized to total protein levels, only calcium and manganese levels were significantly lower in the milk from TMEM165-deficient dams than control dams. These findings suggest that TMEM165 supplies Ca(2+) and Mn(2+) to the Golgi complex in exchange for H(+) to sustain the functions of lactose synthase and potentially other glycosyl-transferases. Our findings highlight the importance of cation and pH homeostasis in the Golgi complex of professional secretory cells and the critical role of TMEM165 in this process. |
| Databáze: | OpenAIRE |
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