Multiple lines of inhibitory feedback on AKT kinase in Schwann cells lacking TSC1/2 hint at distinct functions of mTORC1 and AKT in nerve development
Abstract
During nerve development, Schwann cells (SCs) build multilayered myelin sheaths around axons to accelerate nerve conduction. The mechanistic target of rapamycin complex 1 (mTORC1) downstream of PI3K/AKT signaling lately emerged as a central anabolic regulator of myelination. Using mutant mice with sustained mTORC1 hyperactivity in developing SCs we recently uncovered that mTORC1 impedes developmental myelination by promoting proliferation of immature SCs while antagonizing SC differentiation. In contrast, mTORC1 stimulates myelin production, rather than SC proliferation, in already differentiated SCs. Importantly, these diametrical mTORC1 functions were unmasked under settings of greatly suppressed AKT signaling. Here we demonstrate, inter alia, additional mechanisms of feedback inhibition of AKT by mTORC1, such as strikingly elevated PTEN levels in SCs with disruption of the mTORC1 inhibitory complex, TSC1/2. These data lead us to propose a model wherein mTORC1 and AKT have distinct roles in developing SCs that have to be precisely coordinated for normal myelinogenesis.
References
mTORC1 controls PNS myelination along the mTORC1-RXRγ-SREBP-lipid biosynthesis axis in Schwann cells
Citations
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Brain developing: Influences & Outcomes
This feed focuses on influences that affect the developing brain including genetics, fetal development, prenatal care, and gene-environment interactions. Here is the latest research in this field.
Attention Disorders
Attention is involved in all cognitive activities, and attention disorders are reported in patients with various neurological diseases. Here are the latest discoveries pertaining to attention disorders.
AKT Pathway
This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.