Reciprocal expression regulation of ZIP4 and ZIP5 in intestinal epithelial cells

Abstract

Recent progress in understanding the molecules involved in zinc metabolism have opened a new field of research called “Zinc Biology.” This area of study has received much attention due to its association with several physiopathological events. In contrast, zinc absorption process in the small intestine is relatively less clarified at the molecular level. Molecular understanding of the zinc absorption process and zinc metabolism in the small intestine might possibly lead to the prevention of zinc deficiency and improving human health.

Many zinc transporters are expressed in the intestinal epithelial cells. Of them, ZIP4 and ZIP5 are thought to play pivotal roles in the absorption and homeostatic control of zinc because of their unique expression regulation. ZIP4 localizes to the apical membrane in zinc-deficient conditions and probably contributes to the efficient uptake of zinc into the enterocytes. ZIP5 localizes to the basolateral membrane in zinc excess conditions and possibly contributes to the uptake of zinc from circulation, thus leading to its efflux through gastrointestinal secretion. In this review, we provide an overview of the reciprocal expression regulation of ZIP4 and ZIP5 with a focus on the current progress in our understanding. We also discuss the importance of zinc as an essential nutritional element.