Pathway link LYCHOS-GATOR1

LYCHOS (GPR155) ⊣ GATOR1

LYCHOS (GPR155) inhibits GATOR1.

Cholesterol is a building block the cell needs to grow, so the lysosome keeps track of how much it has. When there is plenty, it sticks to a sensor protein called LYCHOS, which then holds on to GATOR1, the brake that would otherwise stop mTORC1 being pulled to the lysosome. Brake held out of the way, the growth switch gets to work.

When lysosomal cholesterol is high, cholesterol binds the permease-like region of LYCHOS and LYCHOS binds GATOR1 through a conserved cytoplasm-facing loop. Sequestering GATOR1, which is the GTPase-activating protein for the Rag GTPases, keeps that brake off the Rags, so mTORC1 is recruited to the lysosome in a cholesterol- and Rag-dependent way. Mutating the cholesterol-binding site impairs mTORC1 activation (SHI2022).

The conditions it holds under

Single-study edge in this corpus: human cell lines and biochemistry (SHI2022), with the binding interface supported by later cryo-EM structures outside this corpus (Bayly-Jones 2024, PMID 39358511; Zhao 2025, PMID 39824976). No animal or human endpoint, and no measurement of how much of lysosomal cholesterol sensing runs through this route as against the SLC38A9-NPC1 complex (CAS2017), which is a separate cholesterol input to the same machinery.

Time it takes

minutes

Step

direct (one molecule acts on the other)

Measured in

human cells

Where in the cell

lysosome

Reaches people?

plausible in people, not shown directly

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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