Schwann-Cell-Specific Deletion of Phosphatidylinositol 4-Kinase Alpha Causes Aberrant Myelination
| Autor: | Mark Stopfer, Yeun Ju Kim, Takashi Baba, Zane N. Aldworth, Daniel Abebe, Stanko S. Stojilkovic, Alejandro Alvarez-Prats, Ivana Bjelobaba, Tamas Balla |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Phosphatidylinositol 4 5-Diphosphate Schwann cell General Biochemistry Genetics and Molecular Biology Article Cell Line Minor Histocompatibility Antigens 03 medical and health sciences chemistry.chemical_compound Myelin Phosphatidylinositol 3-Kinases Phosphatidylinositol Phosphates Cell Movement medicine Animals Phosphatidylinositol Myelin Sheath Phosphatidylethanolamine Mice Knockout Sphingolipids TOR Serine-Threonine Kinases Cell Membrane Phosphatidylserine Actin cytoskeleton Sciatic Nerve Actins Cell biology Enzyme Activation Phosphotransferases (Alcohol Group Acceptor) 030104 developmental biology medicine.anatomical_structure chemistry nervous system Mutation Schwann Cells Sphingomyelin Proto-Oncogene Proteins c-akt PI4KA Gene Deletion |
| Zdroj: | Cell Rep |
| Popis: | Summary Active membrane remodeling during myelination relies on phospholipid synthesis and membrane polarization, both of which are known to depend on inositol phospholipids. Here, we show that sciatic nerves of mice lacking phosphatidylinositol 4-kinase alpha (PI4KA) in Schwann cells (SCs) show substantially reduced myelin thickness with grave consequences on nerve conductivity and motor functions. Surprisingly, prolonged inhibition of PI4KA in immortalized mouse SCs failed to decrease plasma membrane phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) levels or PI 3-kinase (PI3K) activation, in spite of large reductions in plasma membrane PI4P levels. Instead, it caused rearrangements of the actin cytoskeleton, which was also observed in sciatic nerves of knockout animals. PI4KA inactivation disproportionally reduced phosphatidylserine, phosphatidylethanolamine, and sphingomyelin content in mutant nerves, with similar changes observed in SCs treated with a PI4KA inhibitor. These studies define a role for PI4KA in myelin formation primarily affecting metabolism of key phospholipids and the actin cytoskeleton. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|