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Agonist-induced endocytosis of rat somatostatin receptor 1

Roosterman, D., Kreuzer, O. J., Brune, N., Cottrell, G. S., Bunnett, N. W., Meyerhof, W. and Steinhoff, M. (2007) Agonist-induced endocytosis of rat somatostatin receptor 1. Endocrinology, 148 (3). pp. 1050-1058. ISSN 1945-7170

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To link to this item DOI: 10.1210/en.2006-1600

Abstract/Summary

Somatostatin-receptor 1 (sst1) is an autoreceptor in the central nervous system that regulates the release of somatostatin. Sst1 is present intracellularly and at the cell surface. To investigate sst1 trafficking, rat sst1 tagged with epitope was expressed in rat insulinoma cells 1046-38 (RIN-1046-38) and tracked by antibody labeling. Confocal microscopic analysis revealed colocalization of intracellularly localized rat sst1-human simplex virus (HSV) with Rab5a-green fluorescent protein and Rab11a-green fluorescent protein, indicating the distribution of the receptor in endocytotic and recycling organelles. Somatostatin-14 induced internalization of cell surface receptors and reduction of binding sites on the cell surface. It also stimulated recruitment of intracellular sst1-HSV to the plasma membrane. Confocal analysis of sst1-HSV revealed that the receptor was initially transported within superficial vesicles. Prolonged stimulation of the cells with the peptide agonist induced intracellular accumulation of somatostatin-14. Because the number of cell surface binding sites did not change during prolonged stimulation, somatostatin-14 was internalized through a dynamic process of continuous endocytosis, recycling, and recruitment of intracellularly present sst1-HSV. Accumulated somatostatin-14 bypassed degradation via the endosomal-lysosomal route and was instead rapidly released as intact and biologically active somatostatin-14. Our results show for the first time that sst1 mediates a dynamic process of endocytosis, recycling, and re-endocytosis of its cognate ligand.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
No Reading authors. Back catalogue items
ID Code:30263
Uncontrolled Keywords:Acids/pharmacology Animals Antigens, Surface/drug effects/metabolism Binding Sites Binding, Competitive Cells, Cultured Endocytosis/*drug effects Protein Transport/drug effects Rats Receptors, Somatostatin/*agonists/*metabolism Somatostatin/pharmacokinetics rab GTP-Binding Proteins/physiology
Publisher:Endocrine Society

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