Sphingomyelin metabolism is involved in the maintenance of tissue organization of collecting ducts

FAVALE NICOLAS; SANTACREU BRUNO; PESCIO LUCILA; MARÍA GABRIELA MÁRQUEZ; STERIN-SPEZIALE NORMA B

JLR PAPERS IN PRESS

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Lugar: Bethesda, Maryland; Año: 2015 vol. 2015 p. 786 - 800

0022-2275

Sphingolipids (SLs) are relevant lipid components of eukaryotic cells. Besides regulating various cellular processes, SLs provide the structural framework for plasma membrane organization. Particularly, SM is associated with detergent-resistant microdomains. We have previously shown that the adherens junction (AJ) complex, the relevant cell-cell adhesion structure involved in cell differentiation and tissue organization, is located in an SM-rich membrane lipid domain. We have also demonstrated that under hypertonic conditions, Madin-Darby canine kidney (MDCK) cells acquire a differentiated phenotype with changes in SL metabolism. For these reasons, we decided to evaluate whether SM metabolism is involved in the acquisition of the differentiated phenotype of MDCK cells. We found that SM síntesis mediated by SM synthase 1 is involved in hypertonicityinduced formation of mature AJs, necessary for correct epithelial cell differentiation. Inhibition of SM síntesis impaired the acquisition of mature AJs, evoking a disintegration- like process refl ected by the dissipation of E-cadherin and a- and b-catenins from the AJ complex. As a consequence, MDCK cells did not develop the hypertonicityinduced differentiated epithelial cell phenotype.