The PDZ/coiled-coil domain containing protein PIST modulates insulin secretion in MIN6 insulinoma cells by interacting with somatostatin receptor subtype 5.
The multi-domain protein PIST (protein interacting specifically with Tc10) interacts with the SSTR5 (somatostatin receptor 5) and is responsible for its intracellular localization. Here, we show that PIST is expressed in pancreatic beta-cells and interacts with SSTR5 in these cells. PIST expression in MIN6 insulinoma cells is reduced by somatostatin (SST). After stimulation with SST, SSTR5 undergoes internalization together with PIST. MIN6 cells over-expressing PIST display enhanced glucose-stimulated insulin secretion and a decreased sensitivity to SST-induced inhibition of insulin secretion. These data suggest that PIST plays an important role in insulin secretion by regulating SSTR5 availability at the plasma membrane.
Wente
Wolf
W
Lilly Research Laboratories, Essener Bogen 7, D-22419 Hamburg, Germany.
Efanov
Alexander M
AM
Treinies
Iris
I
Zitzer
Heike
H
Gromada
Jesper
J
Richter
Dietmar
D
Kreienkamp
Hans-Jürgen
HJ
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D007340:Insulinoma; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000819:agonists / Q000032:analysis / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology
D002352:Carrier Proteins; D007328:Insulin; D008565:Membrane Proteins; D017481:Receptors, Somatostatin; D013004:Somatostatin; C094573:somatostatin receptor 5; D005947:Glucose