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Milk biosynthesis requires the Golgi cation exchanger TMEM165
Nathan A Snyder1, Mitchell V Palmer2, Timothy A Reinhardt3
1From the Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218 and.
The Journal of Biological Chemistry
|January 10, 2019
Summary
Transmembrane protein 165 (TMEM165) is essential for milk production in mammals. It maintains Golgi pH, ensuring proper lactose synthesis and offspring growth.
Area of Science:
- Cell Biology
- Mammalian Physiology
- Biochemistry
Background:
- Lactose biosynthesis in the Golgi complex produces H+, potentially disrupting pH homeostasis.
- A mechanism for maintaining physiological pH within the Golgi during milk production is unknown.
Purpose of the Study:
- To investigate the role of the H+/Ca2+/Mn2+ exchanger TMEM165 in mammalian milk production.
- To determine if TMEM165 is crucial for lactose biosynthesis and offspring development.
Main Methods:
- Conditional, tissue-specific knockout mice were utilized.
- Immunostaining and biochemical assays were performed.
- Lactating mammary glands and milk composition were analyzed.
Main Results:
- TMEM165 deficiency impaired lactose biosynthesis and pup growth rates.
- Milk from deficient mice showed increased fat and protein, with reduced Ca2+ and Mn2+ levels.
- TMEM165 appears to facilitate Ca2+ and Mn2+ transport into the Golgi in exchange for H+.
Conclusions:
- TMEM165 is critical for maintaining Golgi cation and pH homeostasis during lactation.
- This homeostasis is vital for the function of lactose synthase and other glycosyltransferases.
- TMEM165 plays a key role in normal milk production and offspring nutrition.
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