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Author Spotlight: Exploring Cellular Zinc Regulation Through ZnT1 Functionality
Published on: June 2, 2023
Influence of ZIP14 (slc39A14) on intestinal zinc processing and barrier function
Gregory J Guthrie1, Tolunay B Aydemir1, Catalina Troche1
1Food Science and Human Nutrition Department and Center for Nutritional Sciences, College of Agricultural and Life Sciences, University of Florida, Gainesville, Florida.
ZIP14 protein influences intestinal permeability by regulating zinc transport. Zip14 knockout mice show impaired gut barrier function and altered tight junction proteins, indicating ZIP14
Area of Science:
- Cell Biology
- Gastroenterology
- Nutritional Science
Background:
- ZIP14 is a zinc transporter highly expressed in the small intestine and liver.
- ZIP14 expression increases during endotoxemia, affecting liver zinc and causing hypozincemia.
- Zinc status and inflammation impact intestinal permeability.
Purpose of the Study:
- To investigate the role of ZIP14 in intestinal zinc metabolism.
- To determine the effect of ZIP14 on intestinal permeability.
- To elucidate ZIP14's mechanism in maintaining intestinal barrier integrity.
Main Methods:
- Utilized wild-type and Zip14 knockout mice.
- Fractionated plasma membranes and isolated endosomes from enterocytes.
- Quantified zinc accumulation and endosomal zinc concentration.
- Assessed intestinal permeability using FITC-dextran and serum endotoxin levels.
- Analyzed tight junction protein phosphorylation and expression (occludin, claudins).
Main Results:
- ZIP14 is localized to the basolateral membrane of enterocytes.
- Zip14 knockout mice exhibited increased zinc accumulation in the small intestine and trapped endosomal zinc.
- Intestinal permeability was significantly greater in Zip14 knockout mice.
- Reduced threonine phosphorylation of occludin and altered claudin expression were observed in knockout mice.
- Impaired tight junction integrity and barrier function were evident in Zip14 knockout jejunum.
Conclusions:
- ZIP14 plays a crucial role in basolateral zinc transport in enterocytes.
- ZIP14 is involved in endosomal zinc trafficking, essential for intestinal barrier function.
- ZIP14 is necessary for maintaining intestinal tight junction integrity and proper gut barrier function.
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