Agonist-dependent Interaction of the Rat Somatostatin Receptor Subtype 2 with Cortactin-binding Protein 1*

  1. Heike Zitzer,
  2. Dietmar Richter§ and
  3. Hans-Jürgen Kreienkamp
  1. From the Institut für Zellbiochemie und klinische Neurobiologie, Universität Hamburg, Martinistrasse 52, 20246 Hamburg, Germany

    Abstract

    We report here an interaction between the C terminus of the rat somatostatin receptor subtype 2 (SSTR2) and a protein that has recently been identified as cortactin-binding protein 1 (CortBP1). Interaction is mediated by the PDZ (PSD-95/discs large/ZO-1) domain of CortBP1. As shown by in situhybridization, SSTR2 and cortactin-binding protein are coexpressed in the rat brain. The association between SSTR2 and the PDZ-domain of CortBP1 was verified by overlay assays and by coprecipitation after transfection in human embryonic kidney (HEK) cells. Analysis by confocal microscopy indicates that CortBP1 is distributed diffusely throughout the cytosol in transfected cells and that it becomes concentrated at the plasma membrane when SSTR2 is present. This process is largely increased when the receptor is stimulated by somatostatin; as CortBP1 interacts with the C terminus of SSTR2, our data suggest that the binding of agonist to the receptor increase the accessibility of the receptor C terminus to the PDZ domain of CortBP1. Our data for the first time establish a link between a G-protein coupled receptor and constituents of the cytoskeleton.

    Footnotes

    • * This work was supported by the Deutsche Forschungsgemeinschaft (SFB545/B7 (to H.-J. K. and D. R.)).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • The data presented here form part of a thesis by H. Z.

    • § To whom correspondence should be addressed: Institut für Zellbiochemie und klinische Neurobiologie, Universität Hamburg, Martinistrasse 52, 20246 Hamburg, Germany. Tel.: 49-40-42803-3344; Fax: 49-40-42803-4541; E-mail: richter{at}uke.uni-hamburg.de.

    • Abbreviations:
      GPCR

      G-protein-coupled receptor

      CortBP1

      cortactin-binding protein 1

      GST

      glutathione S-transferase

      HEK

      human embryonic kidney

      PBS

      phosphate-buffered saline

      PDZ

      PSD-95/discs large/ZO-1

      PSD

      postsynaptic density

      SAP102

      synapse-associated protein 102

      SST

      somatostatin

      SSTR

      somatostatin receptor

      • Received April 14, 1999.
      • Revision received April 29, 1999.
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