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Autocrine Signaling Underlies Fast Repetitive Plasma Membrane Translocation of Conventional and Novel Protein Kinase C Isoforms in beta Cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
2016 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, no 29, 14986-14995 p.Article in journal (Refereed) Published
Abstract [en]

PKC signaling has been implicated in the regulation of many cell functions, including metabolism, cell death, proliferation, and secretion. Activation of conventional and novel PKC isoforms is associated with their Ca2+- and/or diacylglycerol (DAG)-dependent translocation to the plasma membrane. In 13 cells, exocytosis of insulin granules evokes brief (<10 s) local DAG elevations ("spiking") at the plasma membrane because of autocrine activation of P2Y(1), purinoceptors by ATP co-released with insulin. Using total internal reflection microscopy, fluorescent protein -tagged PKCs, and signaling biosensors, we investigated whether DAG spiking causes membrane recruitment of PKCs and whether different classes of PKCs show characteristic responses. Glucose stimulation of MINE cells triggered DAG spiking with concomitant repetitive translocation of the novel isoforms PKCI, PKCE, and PKCirp The conventional PKCa, PKCI3I, and PKC beta II isoforms showed a more complex pattern with both rapid and slow translocation. K+ depolarization-induced PKCE translocation entirely mirrored DAG spiking, whereas PKC beta 1 translocation showed a sustained component, reflecting the subplasma membrane Ca2+ concentration ([Ca2+)pm), with additional effect during DAG spikes. Interference with DAG spiking by purinoceptor inhibition prevented intermittent translocation of PKCs and reduced insulin secretion but did not affect [Ca2+]{,1 elevation or sustained PKCAI translocation. The muscarinic agonist carbachol induced pronounced transient PKCi3I translocation and sustained recruitment of PKCE. When rise of [Ca2+](p), was prevented, the carbachol-induced DAG and PKCE responses were somewhat reduced, but PKCI3I translocation was completely abolished. We conclude that exocytosis-induced DAG spikes efficiently recruit both conventional and novel PKCs to the beta cell plasma membrane. PKC signaling is thus implicated in autocrine regulation of beta cell function.

Place, publisher, year, edition, pages
2016. Vol. 291, no 29, 14986-14995 p.
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-303385DOI: 10.1074/jbc.M115.698456ISI: 000380583200011PubMedID: 27226533OAI: oai:DiVA.org:uu-303385DiVA: diva2:971806
Funder
Swedish Research CouncilNovo NordiskSwedish Diabetes Association
Available from: 2016-09-19 Created: 2016-09-19 Last updated: 2016-09-19Bibliographically approved

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Wuttke, AnneYu, QianTengholm, Anders
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