Beta1 integrins are required for normal CNS myelination and promote AKT-dependent myelin outgrowth.
Oligodendrocytes in the central nervous system (CNS) produce myelin sheaths that insulate axons to ensure fast propagation of action potentials. beta1 integrins regulate the myelination of peripheral nerves, but their function during the myelination of axonal tracts in the CNS is unclear. Here we show that genetically modified mice lacking beta1 integrins in the CNS present a deficit in myelination but no defects in the development of the oligodendroglial lineage. Instead, in vitro data show that beta1 integrins regulate the outgrowth of myelin sheaths. Oligodendrocytes derived from mutant mice are unable to efficiently extend myelin sheets and fail to activate AKT (also known as AKT1), a kinase that is crucial for axonal ensheathment. The inhibition of PTEN, a negative regulator of AKT, or the expression of a constitutively active form of AKT restores myelin outgrowth in cultured beta1-deficient oligodendrocytes. Our data suggest that beta1 integrins play an instructive role in CNS myelination by promoting myelin wrapping in a process that depends on AKT.
Barros
Claudia S
CS
The Scripps Research Institute, Department of Cell Biology, Institute of Childhood and Neglected Disease, La Jolla, CA 92037, USA.
Nguyen
Tom
T
Spencer
Kathryn S R
KS
Nishiyama
Akiko
A
Colognato
Holly
H
Müller
Ulrich
U
D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000648:ultrastructure; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism
D019012:Integrin beta1; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse