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Sci. STKE, 22 April 2003
Vol. 2003, Issue 179, p. re7
[DOI: 10.1126/stke.2003.179.re7]


PDZ Domain Proteins: Plug and Play!

Claire Nourry1, Seth G. N. Grant2, and Jean-Paul Borg1*

1U119 INSERM and Institut Paoli-Calmettes, Laboratory of Molecular Pharmacology, 27 Boulevard Leï Roure, 13009 Marseille, France
2Centre for Neuroscience Research, Division of Neuroscience, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK.

Gloss: PDZ domains (an acronym from PSD-95, Dlg, and ZO-1) are protein modules found in many cytoplasmic proteins (more than 400 in humans); they are discussed in this STKE Review. They are associated with a wide range of other protein-protein interaction domains (for example, WW, PTB, LRR, SH3) or with domains that exhibit particular enzymatic activities (such as guanosine triphosphatases, serine-threonine kinases, phosphatases), and they participate in various intracellular protein networks. PDZ domains bind to very diverse carboxyl-termini of protein partners in a specific (and sometimes reversible) manner, which enables the formation of supramolecular networks. Scaffolding of proteins by PDZ domain proteins usually occurs at specific sites within the cell (such as the plasma membrane or the Golgi apparatus) and is frequently involved in localizing proteins to specialized subcellular compartments of polarized cells, such as the presynaptic terminals and postsynaptic densities of neurons and the basolateral or apical membranes of epithelial cells. Genetic models in invertebrates and vertebrates that are now available for some PDZ proteins illuminate the large set of biological processes in which this protein family is involved, from the establishment and maintenance of the cytoarchitecture to signaling events. Accordingly, defects of PDZ proteins that play a central role in tissue homeostasis result in pathological conditions including cancer and developmental abnormalities. The simplicity of PDZ domain interactions has enabled the design of pharmacological inhibitors of potential therapeutic interest.

*Corresponding author: Telephone, 33-4-91-75-84-09; fax, 33-4-91-26-03-64; e-mail: borg{at}

Citation: C. Nourry, S. G. N. Grant, J.-P. Borg, PDZ Domain Proteins: Plug and Play! Sci. STKE 2003, re7 (2003).

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