Expression, phosphorylation and function of the Rab-GTPase activating protein TBC1D1 in pancreatic beta-cells.
The Rab-GTPase activating protein TBC1D1 is a paralog of AS160/TBC1D4. AS160/TBC1D4, a downstream effector of Akt, has been shown to play a central role in beta-cell function and survival. The two proteins have overlapping function in insulin signalling in muscle cells. However, the expression and the potential role of TBC1D1 in beta-cells remain unknown. Therefore, the aim of this study is to investigate whether TBC1D1 is expressed in beta-cells and whether it plays, as AS160/TBC1D4, a role in beta-cell function and survival. Using human and rat beta-cells, this study shows for the first time that TBC1D1 is expressed and phosphorylated in response to glucose in these cells. Knockdown of TBC1D1 in beta-cells resulted in increased basal and glucose-stimulated insulin release, decreased proliferation but no change in apoptosis.
Department of Genetic Medicine and Development, University Medical Center, University of Geneva, Geneva, Switzerland. Electronic address: sabine.rutti@unige.ch.
Sabine
S
Rütti
Department of Genetic Medicine and Development, University Medical Center, University of Geneva, Geneva, Switzerland.
Caroline
C
Arous
Department of Genetic Medicine and Development, University Medical Center, University of Geneva, Geneva, Switzerland.
Alexandra C
AC
Nica
Department of Biomedical Engineering, Graduate School of Biomedical Engineering, Tohoku University, Japan.
Makoto
M
Kanzaki
Department of Genetic Medicine and Development, University Medical Center, University of Geneva, Geneva, Switzerland.
Philippe A
PA
Halban
Department of Genetic Medicine and Development, University Medical Center, University of Geneva, Geneva, Switzerland.
Karim
K
Bouzakri
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020690:GTPase-Activating Proteins; D007328:Insulin; D011506:Proteins; C526441:TBC1D1 protein, human; C540572:TBC1D1 protein, rat; D005947:Glucose
Apoptosis; Beta-cell; Glucose response; Proliferation; TBC1D1