Agonist-mediated endocytosis of rat somatostatin receptor subtype 3 involves β-arrestin and clathrin coated vesicles

O. J. Kreuzer, B. Krisch, O. Déry, N. W. Bunnett, W. Meyerhof

Research output: Contribution to journalArticle

Abstract

Agonist-induced endocytosis of somatostatin receptors determines subsequent cellular responsiveness to peptide agonist and influences somatostatin receptor scintigraphy, a technique to image various tumours. We examined the internalization of sst3HSV, an epitope-tagged type 3 somatostatin receptor, in transfected rat neuroendocrine insulinoma cells. Stimulation of these cells with somatostatin induced trafficking of coexpressed enhanced green fluorescence protein/β-arrestin 1 fusion protein and sst3HSV to colocalize in the same endocytic vesicles. Coexpression of a dominant negative mutant of the arrestin fusion protein with the receptor blocked the internalization of sst3HSV. Stimulation with somatostatin also induced the transient translocation of α-adaptin, a component of the adaptor protein complex 2, to the plasma membrane. α-adaptin and clathrin colocalized with the receptor. By electron microscopy, we observed internalized sst3 in clathrin coated pits, endosomes and at the limiting membrane of multivesicular bodies, a location typical for receptors being recycled. Concordantly, we observed sst3HSV colocalized with Rab11 in a perinuclear compartment which is likely to correspond to the pericentriolar recycling endosome. Thus, agonist-induced endocytosis of sst3 depends on its interaction with β-arrestin, involves the adaptor protein complex 2 and proceeds via clathrin coated vesicles to the recycling compartment.

Original languageEnglish (US)
Pages (from-to)279-287
Number of pages9
JournalJournal of Neuroendocrinology
Volume13
Issue number3
DOIs
StatePublished - 2001

Keywords

  • Arrestin
  • Clathrin
  • Endocytosis
  • Receptor
  • Somatostatin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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