Vacuoles provide the source membrane for TORC1-containing signaling endosomes

Area of Science:

• Eukaryotic cell biology
• Organelle biogenesis
• Cell signaling

Background:

• Signaling endosomes are crucial platforms for the Target of Rapamycin Complex 1 (TORC1) kinase.
• TORC1 regulates cellular metabolism, but signaling endosome generation remained unknown.
• Understanding organelle biogenesis is fundamental to cell biology.

Purpose of the Study:

• To elucidate the mechanisms and molecular players involved in signaling endosome biogenesis.
• To investigate the membrane source and regulatory factors for de novo signaling endosome formation.

Main Methods:

• Developed a system for synchronized de novo signaling endosome formation.
• Enabled real-time monitoring of organelle biogenesis.
• Investigated the role of vacuoles and the CROP complex.

Main Results:

• Identified vacuoles as the membrane source for new signaling endosomes.
• Demonstrated that the CROP complex (Atg18 PROPPIN and retromer) mediates vacuole membrane supply.
• Showed that TORC1 activity is required for signaling endosome formation, indicating regulation.

Conclusions:

• Unveiled the first mechanistic principles of signaling endosome biogenesis.
• Identified key molecular participants, including vacuoles, the CROP complex, and TORC1.
• Provided insights into the regulated generation of essential signaling organelles.