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Department of Pharmacology (M.K., X.L., T.H., M.A.), The University of Iowa College of Medicine, Iowa City, Iowa 52242-1109; and Department of Molecular Biology and Genetics (D.R., A.B.), Cornell University, Ithaca, New York 14853-2703
Address all correspondence and requests for reprints to: Dr. Mario Ascoli, Department of Pharmacology, 2–319B BSB, 51 Newton Road, The University of Iowa, Iowa City, IA 52242-1109. E-mail: mario-ascoli{at}uiowa.edu
We show that most of the internalized rat LH receptor is routed to a lysosomal degradation pathway whereas a substantial portion of the human LH receptor is routed to a recycling pathway. Chimeras of these two receptors identified a linear amino acid sequence (GTALL) present near the C terminus of the human LH receptor that, when grafted onto the rat LH receptor, redirects most of the rat LH receptor to a recycling pathway. Removal of the GTALL sequence from the human LH receptor failed to affect its routing, however.
The GTALL sequence shows homology with the C-terminal tetrapeptide (DSLL) of the ß2-adrenergic receptor, a motif that has been reported to mediate the recycling of the internalized ß2-adrenergic receptor by binding to ezrin-radixin-moesin-binding phosphoprotein-50. Addition of the DSLL tetrapeptide to the C terminus of the rat LH receptor also redirects most of the internalized rat LH receptor to a recycling pathway but, like the recycling of the human LH receptor, this rerouting is not mediated by ezrin-radixin-moesin-binding phosphoprotein-50.
We conclude that most of the internalized rat LH receptor is degraded because its C-terminal tail lacks motifs that promote recycling and that two distinct, but homologous, motifs (DSLL at the C terminus or GTALL near the C terminus) can reroute the internalized rat LH receptor to a recycling pathway that is independent of ezrin-radixin-moesin-binding phosphoprotein-50.
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