TORC2 controls endocytosis through plasma membrane tension

Area of Science:

• Cell Biology
• Biophysics
• Molecular Biology

Background:

• Target of rapamycin complex 2 (TORC2) is a key protein kinase regulating plasma membrane (PM) dynamics.
• TORC2 influences crucial cellular processes like endocytosis, but the mechanisms are not fully understood.
• Previous studies suggest TORC2 signaling involves phosphorylation cascades, but observed kinetics of endocytosis inhibition are slow.

Purpose of the Study:

• To investigate the role of TORC2 in endocytosis beyond simple phosphorylation.
• To explore the impact of TORC2 inhibition on plasma membrane tension and its effect on endocytosis.
• To elucidate the biophysical mechanisms by which TORC2 regulates endocytic events.

Main Methods:

• Chemical inhibition of TORC2 in cellular models.
• Measurement of plasma membrane tension.
• Analysis of protein-actin cytoskeleton interactions during endocytosis.
• Investigation of recruitment dynamics of endocytic proteins like Rvs167.

Main Results:

• TORC2 inhibition leads to increased plasma membrane tension, independent of direct phosphorylation events.
• Elevated PM tension disrupts endocytosis by weakening the interaction between PM adaptor proteins (Sla2, Ent1) and the actin cytoskeleton.
• Increased PM tension hinders the recruitment of Rvs167, a protein crucial for vesicle fission, to endocytic sites.

Conclusions:

• TORC2 regulates endocytosis through both biochemical (phosphorylation) and biophysical (plasma membrane tension) mechanisms.
• Plasma membrane tension serves as a critical biophysical cue in the regulation of endocytosis.
• These findings highlight the importance of integrating biophysical principles into understanding cellular processes.