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Anchoring of protein kinase A-regulatory subunit II alpha to subapically positioned centrosomes mediates apical bile canalicular lumen development in response to oncostatin m but not cAMP

Wojtal, K. A., Hoekstra, D. & van Ijzendoorn, S. C. D., Jul-2007, In : Molecular Biology of the Cell. 18, 7, p. 2745-2754 10 p.

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Oncostatin M and cAMP signaling stimulate apical surface-directed membrane trafficking and apical lumen development in hepatocytes, both in a protein kinase A (PKA)-dependent manner. Here, we show that oncostatin M, but not cAMP, promotes the A-kinase anchoring protein (AKAP)-dependent anchoring of the PKA regulatory subunit (R)II alpha to subapical centrosomes and that this requires extracellular signal-regulated kinase 2 activation. Stable expression of the RII-displacing peptide AKAP-IS, but not a scrambled peptide, inhibits the association of RII alpha with centrosomal AKAPs and results in the repositioning of the centrosome from a subapical to a perinuclear location. Concomitantly, common endosomes, but not apical recycling endosomes, are repositioned from a subapical to a perinuclear location, without significant effects on constitutive or oncostatin M-stimulated basolateral-to-apical transcytosis. Importantly, however, the expression of the AKAP-IS peptide completely blocks oncostatin M-, but not cAMP-stimulated apical lumen development. Together, the data suggest that centrosomal anchoring of RII alpha and the interrelated subapical positioning of these centrosomes is required for oncostatin M-, but not cAMP-mediated, bile canalicular lumen development in a manner that is uncoupled from oncostatin M-stimulated apical lumen-directed membrane trafficking. The results also imply that multiple PKA-mediated signaling pathways control apical lumen development and that subapical centrosome positioning is important in some of these pathways.

Original languageEnglish
Pages (from-to)2745-2754
Number of pages10
JournalMolecular Biology of the Cell
Volume18
Issue number7
Publication statusPublished - Jul-2007

    Keywords

  • CANINE KIDNEY-CELLS, POLARIZED SPHINGOLIPID TRANSPORT, RAT HEPATOCYTE COUPLETS, HEPG2 CELLS, EPITHELIAL-CELLS, MICROTUBULE ORGANIZATION, MEMBRANE BIOGENESIS, SIGNAL-TRANSDUCTION, RECYCLING SYSTEM, MDCK CELLS

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