Rag GTPases / Ragulator complex

Classification

Category: Upstream regulator (amino-acid sensing, GTPase heterodimer + scaffold)

Aliases: RagA/B/C/D, Ragulator (LAMTOR complex)

Relationship to mTOR complexes: Upstream of mTORC1 (amino-acid branch) — see mTORC1 vs mTORC2 for the full complex-level map.

Summary

The Rag GTPase heterodimers, anchored to the lysosomal membrane by the Ragulator scaffold complex, sense amino-acid sufficiency and recruit mTORC1 to the lysosomal surface -- the site where active Rheb can engage it. This is the amino-acid-sensing branch of mTORC1 regulation, distinct from the growth-factor (AKT/TSC/Rheb) branch.

• Amino-acid sufficiency (sensed via multiple amino-acid sensors) promotes the active Rag GTPase conformation
• Leucine specifically signals via Sestrin2, which relieves GATOR2 inhibition of GATOR1, which otherwise acts as a GAP to inactivate the Rag GTPases
• Dietary protein restriction and specific amino-acid (e.g. BCAA) restriction reduce this input -- see /protein-restriction, /bcaa-restriction, /isoleucine-restriction

• Recruits mTORC1 to the lysosomal membrane, where it can be engaged and activated by Rheb-GTP

• Rag/Ragulator localization and Rheb activation are both required for full mTORC1 activity in the canonical model -- amino-acid sufficiency (Rag) and growth-factor/energy status (Rheb via TSC1/2) are parallel, jointly-necessary inputs.
• Leucine -> Sestrin2 -> GATOR2/GATOR1 -> Rag is the specific molecular route by which a single amino acid (leucine) signals to this complex, distinguishing it from the broader Rag-activating effect of general amino-acid sufficiency.

Source tier

Tier 2 · Biological synthesis (author-cluster reviews, not primary trial data) Reference synthesis attributed in the brief to the Saxton & Sabatini; Laplante & Sabatini; and Liu & Sabatini mTOR review literature (author-cluster attribution, tier 2, brief §4). Exact article-level PMID/DOI not supplied in the sourcing brief and is not fabricated here.