PIKE is essential for oligodendroglia development and CNS myelination.
Oligodendrocyte (OL) differentiation and myelin development are complex events regulated by numerous signal transduction factors. Here, we report that phosphoinositide-3 kinase enhancer L (PIKE-L) is required for OL development and myelination. PIKE-L expression is up-regulated when oligodendrocyte progenitor cells commit to differentiation. Conversely, depleting phosphoinositide-3 kinase enhancer (PIKE) expression by shRNA prevents oligodendrocyte progenitor cell differentiation. In both conventional PIKE knockout (PIKE(-/-)) and OL-specific PIKE knockout mice, the number of OLs is reduced in the corpus callosum. PIKE(-/-) OLs also display defects when forming myelin sheath on neuronal axons during neonatal development, which is partially rescued when PTEN is ablated. In addition, Akt/mTOR signaling is impaired in OL-enriched tissues of the PIKE(-/-) mutant, leading to reduced expression of critical proteins for myelin development and hypomyelination. Moreover, myelin repair of lysolecithin-induced lesions is delayed in PIKE(-/-) brain. Thus, PIKE plays pivotal roles to advance OL development and myelinogenesis through Akt/mTOR activation.
Department of Pathology and Laboratory Medicine, Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322.
Chi Bun
CB
Chan
Xia
X
Liu
Lixia
L
Zhao
Guanglu
G
Liu
Chi Wai
CW
Lee
Yue
Y
Feng
Keiqang
K
Ye
D000818:Animals; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000254:growth & development / Q000473:pathology / Q000648:ultrastructure; D002452:Cell Count; D002478:Cells, Cultured; D002490:Central Nervous System / Q000254:growth & development / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015854:Up-Regulation
D009419:Nerve Tissue Proteins; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C418731:Agap2 protein, rat; D020558:GTP Phosphohydrolases; C529781:PIKE protein, mouse; D020559:Monomeric GTP-Binding Proteins