Schwann-Cell-Specific Deletion of Phosphatidylinositol 4-Kinase Alpha Causes Aberrant Myelination.

ABSTRACT: 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 inactiv

SUBMITTER: Alvarez-Prats A 

PROVIDER: S-EPMC7268203 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature