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| Subject Categories: Membranes & Transport | Signal Transduction |
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| The EMBO Journal
(2002) 21, 6409–6418, doi: 10.1093/emboj/cdf629 |
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| Oncostatin M regulates membrane traffic and stimulates bile canalicular membrane biogenesis in HepG2 cells |
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| Johanna M. van der Wouden, Sven C.D. van IJzendoorn and Dick Hoekstra |
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Department of Membrane Cell Biology, University of Groningen, Antonius Deusinglaan 1, 9713AV Groningen, The Netherlands To whom correspondence should be addressed Dick Hoekstra, d.hoekstra@med.rug.nl Received 27 May 2002; Revised 4 October 2002; Accepted 4 October 2002. |
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| Abstract |
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| Hepatocytes are the major epithelial cells of the liver and they display membrane polarity: the sinusoidal membrane representing the basolateral surface, while the bile canalicular membrane is typical of the apical membrane. In polarized HepG2 cells an endosomal organelle, SAC, fulfills a prominent role in the biogenesis of the canalicular membrane, reflected by its ability to sort and redistribute apical and basolateral sphingolipids. Here we show that SAC appears to be a crucial target for a cytokine-induced signal transduction pathway, which stimulates membrane transport exiting from this compartment promoting apical membrane biogenesis. Thus, oncostatin M, an IL-6-type cytokine, stimulates membrane polarity development in HepG2 cells via the gp130 receptor unit, which activates a protein kinase A-dependent and sphingomyelin-marked membrane transport pathway from SAC to the apical membrane. To exert its signal transducing function, gp130 is recruited into detergent-resistant membrane microdomains at the basolateral membrane. These data provide a clue for a molecular mechanism that couples the biogenesis of an apical plasma membrane domain to the regulation of intracellular transport in response to an extracellular, basolaterally localized stimulus. |
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| Keywords: apical plasma membrane, HepG2 cell, oncostatin M, sphingomyelin, subapical compartment |
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