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Weak membrane interactions allow rheb to activate mTORC1 signaling without major lysosome enrichment.

08:00 EDT 18th September 2019 | BioPortfolio

Summary of "Weak membrane interactions allow rheb to activate mTORC1 signaling without major lysosome enrichment."

Stable localization of the Rheb GTPase to lysosomes is thought to be required for activation of mTORC1 signaling. However, the lysosome targeting mechanisms for Rheb remain unclear. We therefore investigated the relationship between Rheb subcellular localization and mTORC1 activation. Surprisingly, we found that Rheb was undetectable at lysosomes. Nonetheless, functional assays in knockout human cells revealed that farnesylation of the C-terminal CaaX motif on Rheb was essential for Rheb-dependent mTORC1 activation. Although farnesylated Rheb exhibited partial endoplasmic reticulum localization, constitutively targeting Rheb to ER membranes did not support mTORC1 activation. Further systematic analysis of Rheb lipidation revealed that weak, non-selective, membrane interactions support Rheb-dependent mTORC1 activation without the need for a specific lysosome targeting motif. Collectively, these results argue against stable interactions of Rheb with lysosomes and instead that transient membrane interactions optimally allow Rheb to activate mTORC1 signaling. [Media: see text].

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This article was published in the following journal.

Name: Molecular biology of the cell
ISSN: 1939-4586
Pages: mbcE19030146

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Medical and Biotech [MESH] Definitions

The interactions of particles responsible for their scattering and transformations (decays and reactions). Because of interactions, an isolated particle may decay into other particles. Two particles passing near each other may transform, perhaps into the same particles but with changed momenta (elastic scattering) or into other particles (inelastic scattering). Interactions fall into three groups: strong, electromagnetic, and weak. (From McGraw-Hill Encyclopedia of Science & Technology, 7th ed)

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