Functionally Distinct PI 3-Kinase Pathways Regulate Myelination in the Peripheral Nervous System
Bradley A. Heller;Monica Ghidinelli;Jakob Voelkl;Steven Einheber;Ryan Smith;Ethan Grund;Grant Morahan;David Chandler;Luba Kalaydjieva;Filippo Giancotti;Rosalind H. King;Aniko Naray Fejes-Toth;Gerard Fejes-Toth;Maria Laura Feltri;Florian Lang;James L. Salzer
Abstract
Functionally and spatially distinct PI 3-K pathways act either early to promote myelination downstream of axonal Neuregulin1 or late to inhibit myelination downstream of α6β4 integrin and Sgk1.The PI 3-kinase (PI 3-K) signaling pathway is essential for Schwann cell myelination. Here we have characterized PI 3-K effectors activated during myelination by probing myelinating cultures and developing nerves with an antibody that recognizes phosphorylated substrates for this pathway. We identified a