Conserved regulators of Rag GTPases orchestrate amino acid-dependent TORC1 signaling

Area of Science:

• Cellular Biology
• Molecular Signaling
• Metabolism and Disease

Background:

• The target of rapamycin complex 1 (TORC1) is a central regulator of cell growth, proliferation, and metabolism.
• TORC1 deregulation is implicated in human pathologies, including cancers and metabolic disorders.
• Amino acid availability is a critical stimulus for TORC1 activation.

Purpose of the Study:

• To review the major known modulators of Rag GTPases, the key mediators of amino acid sensing by TORC1.
• To focus on recent mechanistic insights into the evolutionary conservation and divergence of amino acid signaling pathways.

Main Methods:

• Review of existing literature and recent mechanistic studies.
• Focus on model systems including yeast, flies, and mammals.
• Analysis of conserved and divergent mechanisms in Rag GTPase regulation.

Main Results:

• Rag GTPases, as heterodimeric complexes on lysosomal/vacuolar membranes, communicate amino acid sufficiency to TORC1.
• Numerous conserved modulators of Rag GTPases have been identified across different species.
• Recent studies provide mechanistic insights into the regulation of Rag GTPase guanine nucleotide loading status.

Conclusions:

• Understanding Rag GTPase modulators is essential for comprehending TORC1-mediated amino acid sensing.
• Evolutionary conservation and divergence in these pathways offer insights into fundamental growth control mechanisms.
• Further research into TORC1 signaling holds potential for therapeutic interventions in related human diseases.