Crossref journal-article
Rockefeller University Press
The Journal of Cell Biology (291)
Abstract

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.

Bibliography

Kachinsky, A. M., Froehner, S. C., & Milgram, S. L. (1999). A PDZ-containing Scaffold Related to the Dystrophin Complex at the Basolateral Membrane of Epithelial Cells. The Journal of Cell Biology, 145(2), 391–402.

Authors 3
  1. Amy M. Kachinsky (first)
  2. Stanley C. Froehner (additional)
  3. Sharon L. Milgram (additional)
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Dates
Type When
Created 23 years, 1 month ago (July 26, 2002, 12:45 p.m.)
Deposited 2 years, 1 month ago (July 28, 2023, 8:18 p.m.)
Indexed 1 week, 2 days ago (Aug. 23, 2025, 12:59 a.m.)
Issued 26 years, 4 months ago (April 19, 1999)
Published 26 years, 4 months ago (April 19, 1999)
Published Online 26 years, 4 months ago (April 19, 1999)
Published Print 26 years, 4 months ago (April 19, 1999)
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@article{Kachinsky_1999, title={A PDZ-containing Scaffold Related to the Dystrophin Complex at the Basolateral Membrane of Epithelial Cells}, volume={145}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.145.2.391}, DOI={10.1083/jcb.145.2.391}, number={2}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Kachinsky, Amy M. and Froehner, Stanley C. and Milgram, Sharon L.}, year={1999}, month=apr, pages={391–402} }