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© The Rockefeller University Press, 0021-9525/1999//391 $5.00
The Journal of Cell Biology, Volume 145, Number 2, , 1999 391-402

A PDZ-containing Scaffold Related to the Dystrophin Complex at the Basolateral Membrane of Epithelial Cells

Department of Cell and Molecular Physiology and Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545

Membrane scaffolding complexes are key features of many cell types, serving as specialized links between the extracellular matrix and the actin cytoskeleton. An important scaffold in skeletal muscle is the dystrophin-associated protein complex. One of the proteins bound directly to dystrophin is syntrophin, a modular protein comprised entirely of interaction motifs, including PDZ (protein domain named for PSD-95, discs large, ZO-1) and pleckstrin homology (PH) domains. In skeletal muscle, the syntrophin PDZ domain recruits sodium channels and signaling molecules, such as neuronal nitric oxide synthase, to the dystrophin complex. In epithelia, we identified a variation of the dystrophin complex, in which syntrophin, and the dystrophin homologues, utrophin and dystrobrevin, are restricted to the basolateral membrane. We used exogenously expressed green fluorescent protein (GFP)-tagged fusion proteins to determine which domains of syntrophin are responsible for its polarized localization. GFP-tagged full-length syntrophin targeted to the basolateral membrane, but individual domains remained in the cytoplasm. In contrast, the second PH domain tandemly linked to a highly conserved, COOH-terminal region was sufficient for basolateral membrane targeting and association with utrophin. The results suggest an interaction between syntrophin and utrophin that leaves the PDZ domain of syntrophin available to recruit additional proteins to the epithelial basolateral membrane. The assembly of multiprotein signaling complexes at sites of membrane specialization may be a widespread function of dystrophin-related protein complexes.

Key Words: syntrophin • utrophin • dystrobrevin • Madin-Darby canine kidney • green fluorescent protein

Abbreviations used in this paper: DAPC, dystrophin-associated protein complex; ECM, extracellular matrix; GFP, green fluorescent protein; GFP-FL, GFP fused to NH₂ terminus of full-length β2-syntrophin; HB, homogenization buffer; nNOS, neuronal nitric oxide synthase; PDZ, protein domain named for PSD-95, discs large, ZO-1; PH, pleckstrin homology; SU, syntrophin unique; TJ, tight junction.

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