SPHK1/sphingosine kinase 1-mediated autophagy differs between neurons and SH-SY5Y neuroblastoma cells
| Autor: | Ndidi-Ese Uzor, Andrey S. Tsvetkov, Steven Finkbeiner, Jose Felix Moruno Manchon |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Light sphingosine kinase 1 Cellular differentiation Endocytic cycle neurons Apoptosis SH-SY5Y cells Neuroblastoma chemistry.chemical_compound 0302 clinical medicine Sphingosine Phagosomes Phosphorylation Cells Cultured Neurons Cultured Tumor neurodegeneration Cell Differentiation Lipids Endocytosis Cell biology Phosphotransferases (Alcohol Group Acceptor) Sphingosine kinase 1 Neurological Signal Transduction autophagy Biochemistry & Molecular Biology Cell Survival Endosome Cells Green Fluorescent Proteins Endosomes Biology BAG3 Cell Line 03 medical and health sciences Cell Line Tumor Autophagy Animals Humans Molecular Biology Cell Membrane Autophagosomes Neurosciences Cell Biology Addendum Rats 030104 developmental biology nervous system chemistry Cancer cell biology.protein Biochemistry and Cell Biology Lysophospholipids Lysosomes 030217 neurology & neurosurgery |
| Zdroj: | Autophagy, vol 12, iss 8 |
| ISSN: | 1554-8635 1554-8627 |
| DOI: | 10.1080/15548627.2016.1183082 |
| Popis: | Although implicated in neurodegeneration, autophagy has been characterized mostly in yeast and mammalian non-neuronal cells. In a recent study, we sought to determine if SPHK1 (sphingosine kinase 1), implicated previously in macroautophagy/autophagy in cancer cells, regulates autophagy in neurons. SPHK1 synthesizes sphingosine-1-phosphate (S1P), a bioactive lipid involved in cell survival. In our study, we discovered that, when neuronal autophagy is pharmacologically stimulated, SPHK1 relocalizes to the endocytic and autophagic organelles. Interestingly, in non-neuronal cells stimulated with growth factors, SPHK1 translocates to the plasma membrane, where it phosphorylates sphingosine to produce S1P. Whether SPHK1 also binds to the endocytic and autophagic organelles in non-neuronal cells upon induction of autophagy has not been demonstrated. Here, we determined if the effect in neurons is operant in the SH-SY5Y neuroblastoma cell line. In both non-differentiated and differentiated SH-SY5Y cells, a short incubation of cells in amino acid-free medium stimulated the formation of SPHK1-positive puncta, as in neurons. We also found that, unlike neurons in which these puncta represent endosomes, autophagosomes, and amphisomes, in SH-SY5Y cells SPHK1 is bound only to the endosomes. In addition, a dominant negative form of SPHK1 was very toxic to SH-SY5Y cells, but cultured primary cortical neurons tolerated it significantly better. These results suggest that autophagy in neurons is regulated by mechanisms that differ, at least in part, from those in SH-SY5Y cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|