Zinc networks: the cell-specific compartmentalization of zinc for specialized functions (original) (raw)

Abstract

Zinc (Zn2+) is the most abundant trace element in cells and is essential for a vast number of catalytic, structural, and regulatory processes. Mounting evidence indicates that like calcium (Ca2+), intracellular Zn2+ pools are redistributed for specific cellular functions. This occurs through the regulation of 24 Zn2+ transporters whose localization and expression is tissue and cell specific. We propose that the complement and regulation of Zn2+ transporters expressed within a given cell type reflects the function of the cell itself and comprises a ‘Zn2+ network.’ Importantly, increasing information implicates perturbations in the Zn2+ network with metabolic consequences and disease. Herein, we discuss our current understanding of Zn2+ transporters from the perspective of a Zn2+ network in four specific tissues with unique Zn2+ requirements (mammary gland, prostate, pancreas, and brain). Delineating the entire Zn2+ transporting network within the context of unique cellular Zn2+ needs is important in identifying critical gaps in our knowledge and improving our understanding of the consequences of Zn2+ dysregulation in human health and disease.

Corresponding author

About the authors

Stephen R. Hennigar

Stephen R. Hennigar received his MS in Nutritional Sciences at the University of New Hampshire. His Master’s thesis investigated the effects of environmental pollutants on immune function. During his studies, he gained an appreciation for metal metabolism while working in the laboratory of Dr. James McClung at the US Army Research Institute of Environmental Medicine. Stephen is currently a PhD student in Dr. Kelleher’s laboratory in the Department of Nutritional Sciences at The Pennsylvania State University. Stephen’s research aims to understand how zinc regulates mammary gland involution. More specifically, his research focuses on how zinc regulates programmed cell death in the mammary gland and how factors such as cytokines regulate this process.

Shannon L. Kelleher

Dr. Shannon L. Kelleher received her PhD from the Department of Nutrition at the University of California Davis and is currently an Associate Professor in the Department of Nutritional Sciences, Surgery and Cell and Molecular Physiology at The Pennsylvania State University. Her background is in the fields of maternal and infant health, nutrition, and mammary gland biology with an emphasis in trace element biology and human health. She has a broad background and specific research training in nutritional biochemistry, cell and molecular biology, and lactation physiology. Dr. Kelleher’s research program aims to understand how the mammary gland regulates zinc metabolism to optimize mammary gland function. Specifically, her research explores the function, regulation, and integration of the mechanisms through which the mammary gland regulates the acquisition, sequestration, and secretion of zinc during lactation and the contribution of zinc dysregulation to breast disease and cancer.

Received: 2012-2-24

Accepted: 2012-4-13

Published Online: 2012-07-01

Published in Print: 2012-07-01