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

J Neuroendocrinol. 2001 Mar;13(3):279-87. doi: 10.1046/j.1365-2826.2001.00630.x.


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/beta-arrestin1 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 alpha-adaptin, a component of the adaptor protein complex 2, to the plasma membrane. alpha-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 beta-arrestin, involves the adaptor protein complex 2 and proceeds via clathrin coated vesicles to the recycling compartment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Protein Complex alpha Subunits
  • Adaptor Proteins, Vesicular Transport
  • Animals
  • Arrestins / genetics
  • Arrestins / physiology*
  • Clathrin-Coated Vesicles / physiology*
  • Endocytosis / drug effects*
  • Endosomes / chemistry
  • Endosomes / metabolism
  • Fluorescent Antibody Technique
  • Green Fluorescent Proteins
  • Immunohistochemistry
  • Insulinoma
  • Luminescent Proteins / genetics
  • Membrane Proteins / metabolism
  • Microscopy, Electron
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Mutation
  • Pancreatic Neoplasms
  • Rats
  • Receptors, Somatostatin / analysis
  • Receptors, Somatostatin / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Somatostatin / pharmacology
  • Transfection
  • Tumor Cells, Cultured
  • beta-Arrestins
  • rab GTP-Binding Proteins / analysis


  • Adaptor Protein Complex alpha Subunits
  • Adaptor Proteins, Vesicular Transport
  • Arrestins
  • Luminescent Proteins
  • Membrane Proteins
  • Receptors, Somatostatin
  • Recombinant Fusion Proteins
  • beta-Arrestins
  • somatostatin receptor 3
  • Green Fluorescent Proteins
  • Somatostatin
  • rab11 protein
  • rab GTP-Binding Proteins