| First Author | Pituch KC | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 11 | Pages | 7040-53 |
| PubMed ID | 25605750 | Mgi Jnum | J:220025 |
| Mgi Id | MGI:5632044 | Doi | 10.1074/jbc.M115.636498 |
| Citation | Pituch KC, et al. (2015) Dysfunction of Platelet-derived Growth Factor Receptor alpha (PDGFRalpha) Represses the Production of Oligodendrocytes from Arylsulfatase A-deficient Multipotential Neural Precursor Cells. J Biol Chem 290(11):7040-53 |
| abstractText | The membrane-bound receptor for platelet-derived growth factor A (PDGFRalpha) is crucial for controlling the production of oligodendrocytes (OLs) for myelination, but regulation of its activity during OL differentiation is largely unknown. We have examined the effect of increased sulfated content of galactosylceramides (sulfatides) on the regulation of PDGFRalpha in multipotential neural precursors (NPs) that are deficient in arylsulfatase A (ASA) activity. This enzyme is responsible for the lysosomal hydrolysis of sulfatides. We show that sulfatide accumulation significantly impacts the formation of OLs via deregulation of PDGFRalpha function. PDGFRalpha is less associated with detergent-resistant membranes in ASA-deficient cells and showed a significant decrease in AKT phosphorylation. Rescue experiments with ASA showed a normalization of the ratio of long versus short sulfatides, restored PDGFRalpha levels, corrected its localization to detergent-resistant membranes, increased AKT phosphorylation, and normalized the production of OLs in ASA-deficient NPs. Moreover, our studies identified a novel mechanism that regulates the secretion of PDGFRalpha in NPs, in glial cells, and in the brain cortex via exosomal shedding. Our study provides a first step in understanding the role of sulfatides in regulating PDGFRalpha levels in OLs and its impact in myelination. |
