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Volume 272, Number 30, Issue of July 25, 1997 pp. 19035-19045
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Disruption of Microtubules Reveals Two Independent Apical Targeting Mechanisms for G-protein-coupled Receptors in Polarized Renal Epithelial Cells

(Received for publication, March 17, 1997, and in revised form, May 20, 1997)

From the Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232

G-protein-coupled receptors demonstrate differing trafficking itineraries in polarized Madin-Darby canine kidney (MDCK II) cells. The _2A adrenergic receptor (_2AAR) is directly delivered to the basolateral subdomain; the A₁ adenosine receptor (A₁AdoR) is apically enriched in its targeting; and the _2BAR subtype is randomly delivered to both domains but selectively retained basolaterally (Keefer, J. R., and Limbird, L. E. (1993) J. Biol. Chem. 268, 11340-11347; Saunders, C., Keefer, J. R., Kennedy, A. P., Wells, J. N., and Limbird, L. E. (1996) J. Biol. Chem. 271, 995-1002; Wozniak, M., and Limbird, L. E. (1996) J. Biol. Chem. 271, 5017-5024). The present studies explore the role of the polarized cytoskeleton in localization of G-protein-coupled receptors in MDCK II cells. Nocodazole or colchicine, which disrupt microtubules, did not perturb lateral localization of ₂AR subtypes but led to a relocalization the A₁AdoR to the basolateral surface, revealed by immunocytochemical and metabolic labeling strategies. Conversely, the apical component of the random delivery of _2BAR was not affected by these agents, suggesting microtubule-dependent and -independent apical targeting mechanisms for G-protein-coupled receptors in polarized cells. Apparent rerouting of the apically targeted A₁AdoR was selective for microtubule-disrupting agents, since cytochalasin D, which disrupts actin polymerization, did not alter A₁AdoR or _2BAR localization or targeting. These data suggest that multiple apical targeting mechanisms exist for G-protein-coupled receptors and that microtubule-disrupting agents serve as tools to probe their different trafficking mechanisms.

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