Crosstalk of the group IIa and IIb metals calcium and zinc in cellular signaling
Year: 2001
Type: article
Abstract: Life has harnessed the functional potential of many metal ions and thereby bridged the boundaries between organic and inorganic chemistry. A case in point here is zinc, which is essential for growth and development. As a constituent of proteins, zinc performs critical cellular functions (1). Its great versatility in catalysis is used in hundreds of enzymes of all six classes (2). In zinc finger proteins—a generic term for several coordination types in thousands of proteins—it has primarily a structural role in organizing protein domains for the recognition of other proteins, nucleic acids, and lipids (3, 4). A third function, regulation, which requires a dynamic state of the zinc ion, is less well established and is the subject of this commentary. In a recent issue of PNAS, Hershfinkel et al. (5) suggested that a “zinc-sensing receptor” exists on the plasma membrane of HT-29 cells. They challenged these colon cancer cells with zinc and followed cellular calcium with the fluorophore Fura-2. Micromolar concentrations of extracellular zinc (Zn2+)—but not of other metal ions—mobilize intracellular calcium, [Ca2+]i, by releasing it from its store in the endoplasmic reticulum (ER). Because intracellular zinc does not increase, the authors suspect that zinc acts at the cell membrane. Further studies on the possible signal transduction pathway implicate the involvement of a G-protein, phospholipase C (PLC), and inositol 1,4,5-trisphosphate (IP3) receptors on the ER membrane (Fig. 1, pathway A). The effect of zinc on the rise of calcium was confirmed in other human cells, e.g., salivary gland cells and primary keratinocytes. Last but not least, the authors show that the action of zinc is upstream from the known calcium-stimulated Na+/H+ antiporter, which controls cellular pH. They conclude that such a “zinc-sensing receptor” might provide a missing link between …
Author: Wolfgang Maret
Institution: Harvard University
Language: English
Topic: Trace Elements in Health
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2091749240