Sphingomyelin metabolism is involved in the differentiation of MDCK cells induced by environmental hypertonicity

Abstract

This article is available online at http://www.jlr.org differentiation, and intracellular traffi cking ( 1 ). It has been demonstrated that cells adjust SL production in response to metabolic needs ( 2 ). SM is biochemically synthesized through the activity of serine-palmitoyl-CoA transferase, 3-ketosphinganine reductase, ceramide (Cer) synthase, dihydroceramide desaturase, and sphingomyelin synthase (SMS). SMS, which uses Cer and phosphatidylcholine as substrates, is the last enzyme in SM biosynthesis ( 3 ). Two isoforms, SMS1 and SMS2, have been cloned in mammals ( 4 ). SMS1 localizes in the Golgi apparatus, whereas SMS2 can be localized in the PM ( 5 ) but also in the Golgi apparatus. Although SM is principally synthesized by SMS1 activity, it has been reported that both SMS1 and SMS2 are required for SM homeostasis and growth in human HeLa cells ( 6 ). SM synthesis is directly related to correct intracellular protein traffi cking ( 7 ). It has been recently shown that the downregulation of SMSs significantly retards the traffi cking of the reporter protein vesicular stomatitis virus G protein tagged with GFP from the trans-Golgi network to the PM. Moreover, the correct endosomal recycling network is directly related to Golgi SM synthesis ( 8 ).SM is the main SL in mammalian cells. Because of the high affi nity of interaction with cholesterol, SM drives the formation of PM rafts or detergent-resistant microdomains (DRMs) ( 9, 10 ), thus providing a framework for PM organization. Early studies have demonstrated

Changes in ceramide metabolism are essential in Madin-Darby canine kidney cell differentiation

“…We have previously reported that renal collecting duct cells regulate the branching of sphingolipid metabolism depending on the stage of cellular differentiation (25). Further, we demonstrated that, during hypertonicity-induced differentiation, MDCK cells develop a program of sphingolipid metabolism that includes a FB1-resistant increase in GSLs (14) and SM synthesis (15). Consequently, we hypothesized that different CerSs synthesizing different species of sphingolipids could play a role in the process of differentiation.…”

“…In a recent work, we have demonstrated that SM metabolism is also involved in the differentiation of MDCK cells induced by hypertonicity (15). In this work, we were interested in analyzing the molecular species of SM in undifferentiated and differentiated MDCK cells.…”

“…We have previously demonstrated that during the differentiation of Madin-Darby canine kidney (MDCK) cells induced by hypertonicity, cells develop a program of sphingolipid metabolism that includes an increase in GSL and SM synthesis (14,15). This increased production of GSLs is essential to acquire the MDCK cell-differentiated phenotype, reflected by the development of the mature apical membrane domain and the formation of the primary cilium, considered the last steps in the final epithelial cell differentiation.…”

The identification of small molecule inhibitors of the plant inositol phosphorylceramide synthase which demonstrate herbicidal activity

“…These have been shown to be vital for the localization and endocytosis of plasma membrane proteins in S. pombe 3 . In addition, aside from maintaining the structural integrity of the plasma membrane, sphingolipids have been demonstrated to play crucial roles in a number of eukaryotic cell processes including apoptosis 4,5 , cell differentiation 6 , cell cycle arrest 7 , cell signalling 8 , angiogenesis 9 and senescence 10 .…”

Sphingosine kinase and sphingosine-1-phosphate regulate epithelial cell architecture by the modulation of de novo sphingolipid synthesis

“…In fact, cell differentiation is accompanied by an increase in SM synthesis and an increase in C24:0 and C24:1 glucosylceramide (GluCer) generated from the Cer recycling pathway [ 14 – 16 ]. While the increase in SM synthesis is involved in the assembly of a mature adherens junction (AJ) [ 15 ], the development of a differentiated apical membrane domain depends on GluCer synthesis [ 14 ].…”