PT  - JOURNAL ARTICLE
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
TI  - Elevated Phosphatidylinositol 3,4,5-Trisphosphate in Glia Triggers Cell-Autonomous Membrane Wrapping and Myelination
AID  - 10.1523/JNEUROSCI.0219-10.2010
DP  - 2010 Jun 30
TA  - The Journal of Neuroscience
PG  - 8953--8964
VI  - 30
IP  - 26
4099  - http://www.jneurosci.org/content/30/26/8953.short
4100  - http://www.jneurosci.org/content/30/26/8953.full
SO  - J. Neurosci.2010 Jun 30; 30
AB  - 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.