TY - JOUR T1 - Elevated Phosphatidylinositol 3,4,5-Trisphosphate in Glia Triggers Cell-Autonomous Membrane Wrapping and Myelination JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8953 LP - 8964 DO - 10.1523/JNEUROSCI.0219-10.2010 VL - 30 IS - 26 AU - Sandra Goebbels AU - Jan H. Oltrogge AU - Robert Kemper AU - Ingo Heilmann AU - Ingo Bormuth AU - Susanne Wolfer AU - Sven P. Wichert AU - Wiebke Möbius AU - Xin Liu AU - Corinna Lappe-Siefke AU - Moritz J. Rossner AU - Matthias Groszer AU - Ueli Suter AU - Jens Frahm AU - Susann Boretius AU - Klaus-Armin Nave Y1 - 2010/06/30 UR - http://www.jneurosci.org/content/30/26/8953.abstract N2 - In the developing nervous system, constitutive activation of the AKT/mTOR (mammalian target of rapamycin) pathway in myelinating glial cells is associated with hypermyelination of the brain, but is reportedly insufficient to drive myelination by Schwann cells. We have hypothesized that it requires additional mechanisms downstream of NRG1/ErbB signaling to trigger myelination in the peripheral nervous system. Here, we demonstrate that elevated levels of phosphatidylinositol 3,4,5-trisphosphate (PIP3) have developmental effects on both oligodendrocytes and Schwann cells. By generating conditional mouse mutants, we found that Pten-deficient Schwann cells are enhanced in number and can sort and myelinate axons with calibers well below 1 μm. Unexpectedly, mutant glial cells also spirally enwrap C-fiber axons within Remak bundles and even collagen fibrils, which lack any membrane surface. Importantly, PIP3-dependent hypermyelination of central axons, which is observed when targeting Pten in oligodendrocytes, can also be induced after tamoxifen-mediated Cre recombination in adult mice. We conclude that it requires distinct PIP3 effector mechanisms to trigger axonal wrapping. That myelin synthesis is not restricted to early development but can occur later in life is relevant to developmental disorders and myelin disease. ER -