Expression, phosphorylation and function of the Rab-GTPase activating protein TBC1D1 in pancreatic beta-cells

•TBC1D1 is expressed in human and rat beta-cells.•TBC1D1 is phosphorylated in response to glucose.•Knockdown of TBC1D1 resulted in increased basal and glucose-stimulated insulin release.•TBC1D1 is involved in beta-cell proliferation but not in apoptosis. The Rab-GTPase activating protein TBC1D1 is a...

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Vydáno v:FEBS letters Ročník 588; číslo 1; s. 15 - 20
Hlavní autoři: Rütti, Sabine, Arous, Caroline, Nica, Alexandra C., Kanzaki, Makoto, Halban, Philippe A., Bouzakri, Karim
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Elsevier B.V 03.01.2014
Témata:
Animals
Apoptosis
Apoptosis - genetics
Beta-cell
Blotting, Western
Cell Proliferation
Cell Survival - genetics
Cells, Cultured
Gene Expression
glucose
Glucose - pharmacology
Glucose response
GTPase-Activating Proteins - genetics
GTPase-Activating Proteins - metabolism
Humans
insulin
Insulin - metabolism
Insulin Secretion
Insulin-Secreting Cells - drug effects
Insulin-Secreting Cells - metabolism
islets of Langerhans
Male
Microscopy, Confocal
myocytes
phosphorylation
Phosphorylation - drug effects
Proliferation
Proteins
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
RNA Interference
TBC1D1
TBC1D1
Beta-cell
Proliferation
Glucose response
Apoptosis
ISSN:0014-5793, 1873-3468, 1873-3468
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Shrnutí:•TBC1D1 is expressed in human and rat beta-cells.•TBC1D1 is phosphorylated in response to glucose.•Knockdown of TBC1D1 resulted in increased basal and glucose-stimulated insulin release.•TBC1D1 is involved in beta-cell proliferation but not in apoptosis. 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. TBC1D1, glucagon and insulincolocalize by fluorescence microscopy (View interaction)
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0014-5793
1873-3468
1873-3468
DOI:10.1016/j.febslet.2013.10.050