Glycosphingolipid synthesis is essential for MDCK cell differentiation

Pescio, Lucila Gisele; Favale, Nicolás Octavio; Márquez, María G.; Sterín-Speziale, Norma

doi:10.1016/j.bbalip.2012.02.009

Cited by 25 publications

(45 citation statements)

References 45 publications

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“…We have previously demonstrated that even after 72 h at confl uence, MDCK cells are only partially polarized and that they reach the fully differentiated phenotype after 48 h of external hypertonicity ( 25 ). Consistently, in the present study, we showed that after 48 h of confl uence, MDCK cells keep an immature fi broblast-like phenotype, but when subjected to 48 h of hypertonicity, they develop a cobblestone-like phenotype typical of mature epithelial cells.…”

Section: The Alteration In the Acquisition Of The Differentiated Phensupporting

confidence: 77%

“…In fact, we have previously described that GlcCer synthase activity is increased in MDCK cells subjected to hypertonic stress. The increase in GlcCer synthesis was necessary to acquire apical membrane maturation ( 25 ). For this reason, we suggest that the loss of AJ formation by SMS inhibition was due to a decrease in SM level and not to an increase in Cer and/or GlcCer levels.…”

Section: Sms Inhibition and Sms1 Knockdown Impair Aj Assembly: Alteramentioning

confidence: 88%

“…The possible explanation for this was that, in our experimental conditions, MDCK cells were able to use the excess of Cer to form GlcCer. In fact, we have previously described that GlcCer synthase activity increased in MDCK cells and was necessary for apical membrane establishment during differentiation ( 25 ). It is important to note that despite the importance of GlcCer in the differentiation process, the SM levels have to be maintained for correct AJ formation.…”

Section: The Alteration In the Acquisition Of The Differentiated Phenmentioning

confidence: 99%

“…In our lab, we have demonstrated that under hypertonic conditions, MDCK cells acquire a differentiated phenotype with changes in the cellular and nuclear architecture ( 25,26 ), accompanied by changes in lipid metabolism ( 27,28 ). Considering both that AJ plays a central role in epithelial cell differentiation and our previous observation that AJ is located in an SM-rich membrane domain, we decided to evaluate whether SM synthesis is involved in the acquisition of the differentiated phenotype of MDCK cells induced by external hypertonic stress.…”

Section: Lipid Analysismentioning

confidence: 99%

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

Favale

Santacreu

Pescio

et al. 2015

Journal of Lipid Research

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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

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Section: The Alteration In the Acquisition Of The Differentiated Phensupporting

confidence: 77%

Section: Sms Inhibition and Sms1 Knockdown Impair Aj Assembly: Alteramentioning

confidence: 88%

Section: The Alteration In the Acquisition Of The Differentiated Phenmentioning

confidence: 99%

Section: Lipid Analysismentioning

confidence: 99%

See 2 more Smart Citations

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

Favale

Santacreu

Pescio

et al. 2015

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…It was also shown that sulfoglycosphingolipid accretion increased along with the osmolality of the incubation medium, which also increased the mRNA of biosynthetic enzymes. In addition, it has been demonstrated that hypertonicity induces MDCK cell differentiation by regulating glycosphingolipid synthesis and accumulation in the apical membrane of MDCK cells ( 32 ). However, whether hyperosmolality affects phospholipid content and biosynthesis has not yet been determined.…”

Section: Flow Cytometrymentioning

confidence: 99%