Polarized membrane traffic and cell polarity development is dependent on dihydroceramide synthase-regulated sphinganine turnover

Molecular Biology of the Cell
Sven C D van IjzendoornD Hoekstra

Abstract

Sphingoid bases have been implicated in various cellular processes including cell growth, apoptosis and cell differentiation. Here, we show that the regulated turnover of sphingoid bases is crucial for cell polarity development, i.e., the biogenesis of apical plasma membrane domains, in well-differentiated hepatic cells. Thus, inhibition of dihydroceramide synthase or sphinganine kinase activity with fumonisin B1 or N,N-dimethylsphingosine, respectively, dramatically perturbs cell polarity development, which is due to increased levels of sphinganine. Consistently, reduction of free sphinganine levels stimulates cell polarity development. Moreover, dihydroceramide synthase, the predominant enzyme responsible for sphinganine turnover, is a target for cell polarity stimulating cAMP/protein kinase A (PKA) signaling cascades. Indeed, electrospray ionization tandem mass spectrometry analyses revealed a significant reduction in sphinganine levels in cAMP/PKA-stimulated cells. These data suggest that sphinganine turnover is critical for and is actively regulated during HepG2 cell polarity development. Previously, we have identified an apical plasma membrane-directed trafficking pathway from the subapical compartment. This transport pat...Continue Reading

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Citations

May 26, 2009·The Journal of Biological Chemistry·Kacper A WojtalSven C D van Ijzendoorn
Dec 17, 2009·Metabolism: Clinical and Experimental·Jin-young LeeYoung Hye Kwon
Jan 18, 2008·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Kacper A WojtalSven C D van Ijzendoorn
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Apr 26, 2006·Journal of Cell Science·Sven C D van Ijzendoorn

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