Cadherins and NCAM as potential targets in metal toxicity

TY - JOUR

T1 - Cadherins and NCAM as potential targets in metal toxicity

AU - Prozialeck, Walter C.

AU - Grunwald, Gerald B.

AU - Dey, P. Markus

AU - Reuhl, Kenneth R.

AU - Parrish, Alan R.

N1 - Funding Information: Portions of this work were supported by NIH Grants R01 ES06478 to W.C.P., R01 EY06658 to G.B.G., and R01 ES04978 to K.R.R. P.M.D. was supported by Training Grants T32 ES07282 and F32 ES05893. The authors thank Victoria Sears for her help with the manuscript, and the Metals Specialty Section of the Society of Toxicology for sponsoring the symposium.

PY - 2002

Y1 - 2002

N2 - Cell adhesion molecules are cell surface proteins that play critical roles in cell recognition and cell adhesion. These adhesion molecules, which include the cadherins, integrins, occludins, and a variety of immunoglobulin-like molecules, are essential for a wide variety of physiologic processes such as epithelial barrier function, tissue development, learning and memory, and immune responses. In light of the evidence that toxic metals can affect many of these processes, investigators have begun to examine the possibility that cell adhesion molecules may be targets for metal toxicity. This review summarizes the results of recent studies showing that certain cell adhesion molecules, particularly the cadherins family of Ca2+-dependent cell adhesion molecules and the immunoglobulin family of Ca2+-independent cell adhesion molecules, may be important early targets on which toxic metals such as a Cd, Hg, and Pb act to produce their toxic effects. These metals, and in some cases their organic compounds, can target cell adhesion molecules at multiple levels, including protein-protein interactions, post-translational modification, and transcriptional regulation. Moreover, by interfering with the normal function of the cadherin family of cell adhesion molecules, some of these metals may activate the β-catenin nuclear signaling pathway. These studies have provided important new insights into the molecular mechanisms of metal toxicity and have opened several exciting avenues of research.

AB - Cell adhesion molecules are cell surface proteins that play critical roles in cell recognition and cell adhesion. These adhesion molecules, which include the cadherins, integrins, occludins, and a variety of immunoglobulin-like molecules, are essential for a wide variety of physiologic processes such as epithelial barrier function, tissue development, learning and memory, and immune responses. In light of the evidence that toxic metals can affect many of these processes, investigators have begun to examine the possibility that cell adhesion molecules may be targets for metal toxicity. This review summarizes the results of recent studies showing that certain cell adhesion molecules, particularly the cadherins family of Ca2+-dependent cell adhesion molecules and the immunoglobulin family of Ca2+-independent cell adhesion molecules, may be important early targets on which toxic metals such as a Cd, Hg, and Pb act to produce their toxic effects. These metals, and in some cases their organic compounds, can target cell adhesion molecules at multiple levels, including protein-protein interactions, post-translational modification, and transcriptional regulation. Moreover, by interfering with the normal function of the cadherin family of cell adhesion molecules, some of these metals may activate the β-catenin nuclear signaling pathway. These studies have provided important new insights into the molecular mechanisms of metal toxicity and have opened several exciting avenues of research.

KW - Cadherins

KW - Cadmium

KW - Lead

KW - Mercury

KW - Methylmercury

KW - NCAM

KW - Trimethyltin

KW - β-Catenin

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U2 - https://doi.org/10.1006/taap.2002.9422

DO - https://doi.org/10.1006/taap.2002.9422

M3 - Review article

C2 - 12183105

SN - 0041-008X

VL - 182

SP - 255

EP - 265

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

IS - 3

ER -