Fas death receptor enhances endocytic membrane traffic converging into the Golgi region

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• The death receptor Fas/CD95 plays a crucial role in initiating apoptosis.
• Fas signaling engages various cellular organelles, including endosomes, but its precise link to membrane traffic remains unclear.
• Cell-type specific differences in Fas-mediated pathways complicate understanding.

Purpose of the Study:

• To systematically investigate endocytosis pathways involved in Fas signaling.
• To clarify the mechanism of Fas-induced membrane traffic in mature T cells.
• To understand how Fas activation influences endocytic membrane organization and its relation to apoptosis.

Main Methods:

• Systematic investigation of known endocytosis pathways.
• Analysis of Fas activation effects on surface protein internalization in T cells.
• Utilizing Rho GTPases, including CDC42, to study actin regulation.
• Colocalization analysis of membrane markers and active caspases around the Golgi apparatus.

Main Results:

• Fas activation in mature T cells utilizes clathrin-independent endocytic portals.
• These portals mediate rapid internalization of surface proteins like CD59, dependent on Rho GTPases (e.g., CDC42).
• Fas stimulation leads to peri-Golgi accumulation of endocytic membranes, concentrating recycling endosomes.
• Internalized Fas receptor complexes and active caspases colocalize with these peri-Golgi membranes.

Conclusions:

• Fas signaling in T lymphocytes redirects endocytic membrane traffic via clathrin-independent portals.
• This traffic diversion, characterized by peri-Golgi polarization, is linked to Fas-mediated apoptosis.
• The findings reveal a specific mechanism of membrane trafficking in T cells upon Fas engagement.