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Title

Regulation of pancreatic beta-cell insulin secretion by actin cytoskeleton remodelling: role of gelsolin and cooperation with the MAPK signalling pathway

Authors
Tomas, Alejandra
Min, Le
Pessin, J. E.
Published in Journal of Cell Science. 2006, vol. 119, no. Pt 10, p. 2156-2167
Abstract We have previously isolated two MIN6 beta-cell sublines, B1, highly responsive to glucose-stimulated insulin secretion, and C3, markedly refractory (Lilla, V., Webb, G., Rickenbach, K., Maturana, A., Steiner, D. F., Halban, P. A. and Irminger, J. C. (2003) Endocrinology 144, 1368-1379). We now demonstrate that C3 cells have substantially increased amounts of F-actin stress fibres whereas B1 cells have shorter cortical F-actin. Consistent with these data, B1 cells display glucose-dependent actin remodelling whereas, in C3 cells, F-actin is refractory to this secretagogue. Furthermore, F-actin depolymerisation with latrunculin B restores glucose-stimulated insulin secretion in C3 cells. In parallel, glucose-stimulated ERK1/2 activation is greater in B1 than in C3 cells, and is potentiated in both sublines following F-actin depolymerisation. Glucose-activated phosphoERK1/2 accumulates at actin filament tips adjacent to the plasma membrane, indicating that these are the main sites of action for this kinase during insulin secretion. In addition, B1 cell expression of the calcium-dependent F-actin severing protein gelsolin is >100-fold higher than that of C3 cells. Knock-down of gelsolin reduced glucose-stimulated insulin secretion, whereas gelsolin over-expression potentiated secretion from B1 cells. Gelsolin localised along depolymerised actin fibres after glucose stimulation. Taken together, these data demonstrate that F-actin reorganization prior to insulin secretion requires gelsolin and plays a role in the glucose-dependent MAPK signal transduction that regulates beta-cell insulin secretion.
Keywords Actins/ metabolismAnimalsBicyclo Compounds, Heterocyclic/pharmacologyCalcium/metabolismCell Membrane/drug effects/metabolismCytoskeleton/drug effects/ metabolismFluorescent Antibody TechniqueGelsolin/ biosynthesis/geneticsGlucose/pharmacologyInsulin/metabolism/ secretionInsulin-Secreting Cells/drug effects/metabolism/ secretionMAP Kinase Signaling System/ physiologyMaleMiceMice, Inbred C57BLMicroscopy, ConfocalMitogen-Activated Protein Kinase 1/metabolismMitogen-Activated Protein Kinase 3/metabolismRNA InterferenceRatsRats, WistarThiazoles/pharmacologyThiazolidines
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PMID: 16638805
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TOMAS, Alejandra et al. Regulation of pancreatic beta-cell insulin secretion by actin cytoskeleton remodelling: role of gelsolin and cooperation with the MAPK signalling pathway. In: Journal of Cell Science, 2006, vol. 119, n° Pt 10, p. 2156-2167. https://archive-ouverte.unige.ch/unige:9056

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Deposited on : 2010-07-12

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