Regulation of the amount of ceramide-1-phosphate synthesized in differentiated human podocytes

Shamroop Kumar Mallela, Alla Mitrofanova, Sandra Merscher, Alessia Fornoni

Research output: Contribution to journalArticle

Abstract

Sphingolipids have important functions as structural components of cells but they also function as signaling molecules regulating different cellular processes such as apoptosis, cell proliferation, cell migration, cell division and inflammation. Hence, a tight regulation of the sphingolipid homeostasis is essential to maintain proper cellular functions. Mammalian ORMDL proteins are orthologues of the yeast ORM1/2 proteins, which regulate ceramide synthesis in yeast. ORMDL proteins inhibit serine palmitoyltransferase (SPT), the enzyme regulating a rate-limiting step of the sphingolipid pathway to control the levels of ceramides and other sphingolipids. Sphingomyelinase phosphodiesterase like 3b (SMPDL3b) is a glycosylphosphatidylinositol (GPI) anchored protein in the plasma membrane (PM) and determines membrane fluidity in macrophages. We previously showed that differential expression of SMPDL3b alters the availability of Ceramide-1-phosphate (C1P) in human podocytes, which are terminally differentiated cells of the kidney filtration barrier. This observation lead us to investigate if SMPDL3b controls C1P availability in human podocytes by interfering with ceramide kinase (CERK) expression and function. We found that SMPDL3b interacts with CERK and can bind to C1P in vitro. Furthermore, CERK expression is reduced when SMPDL3b expression is silenced. These observations led us to propose that one of the mechanisms by which SMPDL3b influences the amount of C1P available in the podocytes is by interfering with the function of CERK thereby maintaining a balance in the levels of the C1P in podocytes.

Original languageEnglish (US)
Article number158517
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1864
Issue number12
DOIs
StatePublished - Dec 1 2019

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Type 3 Cyclic Nucleotide Phosphodiesterases
Sphingomyelin Phosphodiesterase
Podocytes
Sphingolipids
Ceramides
Serine C-Palmitoyltransferase
Glycosylphosphatidylinositols
Proteins
Membrane Fluidity
Fungal Proteins
Cellular Structures
Cell Division
Cell Movement
ceramide 1-phosphate
Homeostasis
Yeasts
Macrophages
Cell Proliferation
Cell Membrane
Apoptosis

Keywords

  • Ceramide-1-phosphate
  • Podocytes
  • SMPDL3b
  • Sphingolipids

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Regulation of the amount of ceramide-1-phosphate synthesized in differentiated human podocytes. / Mallela, Shamroop Kumar; Mitrofanova, Alla; Merscher, Sandra; Fornoni, Alessia.

In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1864, No. 12, 158517, 01.12.2019.

Research output: Contribution to journalArticle

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