Pathway link RAGULATOR-CGASSTING

Ragulator ⊣ cGAS-STING pathway

Ragulator inhibits cGAS-STING pathway.

Lamtor5 belongs to Ragulator, the lysosome complex that switches mTORC1 on, but this link does not run through mTORC1 as far as the source shows. Lamtor5 grabs the inflammation sensor cGAS and sends it for disposal. When Lamtor5 falls with age in immune cells called macrophages, cGAS builds up and drives inflammation that spreads to neighbouring cells; in mice, moving such macrophages into young animals sped up their ageing. This is one mouse study, so it is not known whether the same happens in people, or whether mTORC1 plays any part.

Lamtor5 binds cGAS directly and routes it for degradation through the ESCRT machinery, so the Ragulator subunit acts as a physical brake on the sensor itself. Age-related decline of Lamtor5 in macrophages leaves cGAS stabilised, and that is sufficient to unleash cGAS-mediated paracrine inflammatory signalling: transferring Lamtor5-deficient macrophages accelerates ageing in young mice, while restoring young macrophages, clearing senescent cells, or applying a small peptide that blocks the Lamtor5/cGAS interface alleviates the phenotype in aged mice.

The conditions it holds under

One mouse study (LV2026), A - animal, and no human data for this link. The abstract reports no mTORC1 or mTORC2 measurement for the cGAS step, so whether mTORC1 signalling contributes at all is untested here rather than established. Macrophage-specific: the conditional knockout is myeloid, and the ageing phenotypes are read out at the organismal level, which is a long inferential chain from one protein interaction.

Time it takes

long exposure (days to weeks)

Step

direct (one molecule acts on the other)

Measured in

mouse

Where in the cell

cytosol

Reaches people?

not tested in people

How settled

emerging, few independent studies

Studies behind it

Points the other way

No study in the Atlas contradicts this link. That means none in this curated set, not none in the literature.

Who has checked this

Checked by

No researcher outside the project has checked this link yet.

Curator sign-off

Not signed off yet. This link was drafted with AI help and has not been reviewed link by link; treat it as a proposal until it is.

Curated by

Oliver Barton, with AI help for drafting; see how links are checked.

“Inhibits” describes the effect on the target's activity, not on how much of it there is.

“How settled” describes how far researchers in the field agree. It is not the same as the sign-off above, which only says whether a named curator has checked this page.

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