Fbxw7 Limits Myelination by Inhibiting mTOR Signaling.

Abstract

Myelin, a specialized, proteolipid-rich membrane that ensheaths and insulates nerve fibers, facilitates the rapid conduction of electrical impulses over long distances. Abnormalities in myelin formation or maintenance result in intellectual and motor disabilities, raising a need for therapeutic strategies designed to promote myelination. The mTOR kinase is a powerful driver of myelination, but the mechanisms that regulate mTOR function in myelination are not well understood. Our studies reveal that Fbxw7, a subunit of a ubiquitin ligase that targets other proteins for degradation, acts as a brake on myelination by limiting mTOR function. These findings suggest that Fbxw7 helps tune the amount of myelin produced during development and raise the possibility that Fbxw7 could be a target of myelin-promoting therapies.