Agonist-induced endocytosis of rat somatostatin receptor 1

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Roosterman, D. ; Kreuzer, O. J. ; Brune, N. ; Cottrell, Graeme S. ; Bunnett, N. W. ; Meyerhof, W. ; Steinhoff, M. (2007)

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.
  • References (44)
    44 references, page 1 of 5

    1. Olias G, Viollet C, Kusserow H, Epelbaum J, Meyerhof W 2004 Regulation and function of somatostatin receptors. J Neurochem 89:1057-1091

    2. Patel YC 1999 Somatostatin and its receptor family. Front Neuroendocrinol 20:157-198

    3. Schonbrunn A 1999 Somatostatin receptors present knowledge and future directions. Ann Oncol 10(Suppl 2):S17-S21

    4. Roosterman D, Glassmeier G, Baumeister H, Scherubl H, Meyerhof W 1998 A somatostatin receptor 1 selective ligand inhibits Ca2 currents in rat insulinoma 1046 -38 cells. FEBS Lett 425:137-140

    5. Nunn C, Cervia D, Langenegger D, Tenaillon L, Bouhelal R, Hoyer D 2004 Comparison of functional profiles at human recombinant somatostatin sst2 receptor: simultaneous determination of intracellular Ca2 and luciferase expression in CHO-K1 cells. Br J Pharmacol 142:150 -160

    6. Cervia D, Fiorini S, Pavan B, Biondi C, Bagnoli P 2002 Somatostatin (SRIF) modulates distinct signaling pathways in rat pituitary tumor cells: negative coupling of SRIF receptor subtypes 1 and 2 to arachidonic acid release. Naunyn Schmiedebergs Arch Pharmacol 365:200 -209

    7. Douziech N, Calvo E, Coulombe Z, Muradia G, Bastien J, Aubin RA, Lajas A, Morisset J 1999 Inhibitory and stimulatory effects of somatostatin on two human pancreatic cancer cell lines: a primary role for tyrosine phosphatase SHP-1. Endocrinology 140:765-777

    8. Buscail L, Delesque N, Esteve JP, Saint-Laurent N, Prats H, Clerc P, Robberecht P, Bell GI, Liebow C, Schally AV 1994 Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2. Proc Natl Acad Sci USA 91:2315-2319

    9. Beaudet A, Greenspun D, Raelson J, Tannenbaum GS 1995 Patterns of expression of SSTR1 and SSTR2 somatostatin receptor subtypes in the hypothalamus of the adult rat: relationship to neuroendocrine function. Neuroscience 65:551-561

    10. Viollet C, Lanneau C, Faivre-Bauman A, Zhang J, Djordjijevic D, Loudes C, Gardette R, Kordon C, Epelbaum J 1997 Distinct patterns of expression and physiological effects of sst1 and sst2 receptor subtypes in mouse hypothalamic neurons and astrocytes in culture. J Neurochem 68:2273-2280

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