Interaction of the human somatostatin receptor 3 with the multiple PDZ domain protein MUPP1 enables somatostatin to control permeability of epithelial tight junctions

Liew, Chong Wee; Vockel, Matthias; Glassmeier, Günter; Brandner, Johanna M.; Fernandez-Ballester, Gregorio J.; Schwarz, Jürgen R.; Schulz, Stefan; Buck, Friedrich; Serrano, Luis; Richter, Dietmar; Kreienkamp, Hans-Jürgen

doi:10.1016/j.febslet.2008.11.048

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Volume 583, Issue 1 , Pages 49-54, 5 January 2009

Interaction of the human somatostatin receptor 3 with the multiple PDZ domain protein MUPP1 enables somatostatin to control permeability of epithelial tight junctions

Edited by Beat Imhof

Chong Wee Liew
- Institut für Zellbiochemie und klinische Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
- Present address: Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
- These authors contributed equally to this manuscript.
Matthias Vockel
- Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
- Klinik und Poliklinik für Dermatologie und Venerologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
- These authors contributed equally to this manuscript.
Günter Glassmeier
- Institut für Angewandte Physiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
Johanna M. Brandner
- Klinik und Poliklinik für Dermatologie und Venerologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
Gregorio J. Fernandez-Ballester
- Computational Biology Programme, EMBL, 69117 Heidelberg, Germany
- Present address: IBMC, Universidad Miguel Hernandez, 03202 Elche, Spain.
Jürgen R. Schwarz
- Institut für Angewandte Physiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
Stefan Schulz
- Institut für Pharmakologie und Toxikologie, Friedrich-Schiller-Universität Jena, 07743 Jena, Germany
Friedrich Buck
- Institut für Zellbiochemie und klinische Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
Luis Serrano
- Computational Biology Programme, EMBL, 69117 Heidelberg, Germany
- Present address: Systems Biology, Center for Genomic Regulation, Barcelona, Spain.
Dietmar Richter
- Institut für Zellbiochemie und klinische Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
Hans-Jürgen Kreienkamp
- Institut für Zellbiochemie und klinische Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
- Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
- Corresponding author. Fax: + 49 40 42803 5138.

Received 26 September 2008; received in revised form 12 November 2008; accepted 18 November 2008. published online 09 December 2008.

Abstract

The presence of heterotrimeric G-proteins at epithelial tight junctions suggests that these cellular junctions are regulated by so far unknown G-protein coupled receptors. We identify here an interaction between the human somatostatin receptor 3 (hSSTR3) and the multiple PDZ protein MUPP1. MUPP1 is a tight junction scaffold protein in epithelial cells, and as a result of the interaction with MUPP1 the hSSTR3 is targeted to tight junctions. Interaction with MUPP1 enables the receptor to regulate transepithelial permeability in a pertussis toxin sensitive manner, suggesting that hSSTR3 can activate G-proteins locally at tight junctions.

Structured summary:

MINT-6800756, MINT-6800770: MUPP1 (uniprotkb:O75970) and hSSTR3 (uniprotkb:P32745) colocalize (MI:0403) by fluorescence microscopy (MI:0416)

MINT-6800587:hSSTR3 (uniprotkb:P32745) physically interacts (MI:0218) with MUPP1 (uniprotkb:O55164) by pull down (MI:0096)

MINT-6800562:hSSTR3 (uniprotkb:P32745) physically interacts (MI:0218) with MUPP1 (uniprotkb:O75970) by two hybrid (MI:0018)

MINT-6800622:hSSTR3 (uniprotkb:P32745) physically interacts (MI:0218) with PIST (uniprotkb: Q9HD26), Hsp70 (uniprotkb:P08107), Maguk p55 (uniprotkb: Q8N3R9), MAGI3 (uniprotkb:Q5TCQ9), ZO-2 (uniprotkb:Q9UDY2), ZO-1 (uniprotkb:Q07157) and MUPP1 (uniprotkb:O55164) by pull down (MI:0096)

MINT-6800607, MINT-6801122:hSSTR3 (uniprotkb:P32745) physically interacts (MI:0218) with MUPP1 (uniprotkb:O75970) by anti bait coimmunoprecipitation (MI:0006)

Abbreviations: GIRK, G-protein gated inwardly rectifying potassium channels, GPCR, G-protein coupled receptor, MDCK, Madin-Darby canine kidney, MUPP1, multiple PDZ domain protein 1, PDZ, PSD-95/discs large/ZO-1, PSD-95, postsynaptic density protein of 95kDa, TER, transepithelial resistance, TJs, tight junctions, SST, somatostatin, SSTR, somatostatin receptor, ZO-1, zonula occludens 1