Phosphorylated S6K1 and 4E-BP1 play different roles in constitutively active Rheb-mediated retinal ganglion cell survival and axon regeneration after optic nerve injury

This study investigates how a protein called Rheb, when always active, affects the survival and regrowth of nerve cells in the retina after injury in mice. Rheb is known to activate a pathway (mTOR) that's important for cell growth and survival. The researchers found that when Rheb is constantly active, it helps these retinal nerve cells survive and regrow their connections (axons). This happens because Rheb influences other proteins (S6K1 and 4E-BP1) that control protein production in the cells. However, S6K1 and 4E-BP1 have different roles: S6K1 promotes both cell survival and axon regrowth, while 4E-BP1 mainly helps with cell survival but needs to be inactive for axon regrowth.

• 1
  Overexpression of constitutively active Rheb promoted survival of retinal ganglion cells in the acute (14 days) and chronic (21 and 42 days) stages of injury.
• 2
  mTORC1-mediated S6K1 activation and 4E-BP1 inhibition were necessary components for constitutively active Rheb-induced axon regeneration.
• 3
  Functional 4E-BP1 and S6K1 are neuroprotective and that 4E-BP1 may exert protective effects through a pathway at least partially independent of Rheb/mTOR.