Farnesylation-defective Rheb Increases Axonal Length Independently of mTORC1 Activity in Embryonic Primary Neurons.

摘要: Rheb (Ras homolog enriched in the brain) is a small GTPase protein that plays an important role cell signaling for development of neocortex through modulation mTORC1 (mammalian-target-of-rapamycin-complex-1) activity. known to control various biological processes including axonal growth forming complexes at lysosomal membrane compartment. As such, anchoring on via farnesylation its cysteine residue (C180) required promotion mTOR To test significance farnesylation, we overexpressed mutant form Rheb, C180S, primary rat hippocampal neurons and also mouse embryonic using utero electroporation. Interestingly, found C180S maintained promotional effect elongation similar wild-type both systems. On other hand, failed exhibit multiple axon-promoting which Rheb. The levels phospho-4EBP1, downstream target mTORC1, were surprisingly increased transfected neurons, despite phosphorylated being significantly decreased compared vector transfectants. A specific inhibitor, rapamycin, could not completely abolish axon characteristics cells. Our data suggests non-membrane compartment can promote phosphorylation 4EBP1 mTORC1-independent pathway.