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Vol. 20, Issue 2, 600-615, January 15, 2009

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Fas Death Receptor Enhances Endocytic Membrane Traffic Converging into the Golgi Region

Mauro Degli Esposti^*, Julien Tour^*, Sihem Ouasti^*, Saska Ivanova, Paola Matarrese, Walter Malorni, and Roya Khosravi-Far

*Faculty of Life Sciences, The University of Manchester, M13 9PT Manchester, United Kingdom; Department of Biochemistry, Structural and Molecular Biology, Jozef Stefan Institute, 1000 Ljubljana, Slovenia; Section of Cell Aging and Degeneration, Department of Drug Research and Evaluation, Istituto Superiore Sanità, 00161 Rome, Italy; and Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215

Submitted September 11, 2008; Revised October 30, 2008; Accepted November 14, 2008
Monitoring Editor: Marcos Gonzalez-Gaitan

The death receptor Fas/CD95 initiates apoptosis by engaging diverse cellular organelles including endosomes. The link between Fas signaling and membrane traffic has remained unclear, in part because it may differ in diverse cell types. After a systematic investigation of all known pathways of endocytosis, we have clarified that Fas activation opens clathrin-independent portals in mature T cells. These portals drive rapid internalization of surface proteins such as CD59 and depend upon actin-regulating Rho GTPases, especially CDC42. Fas-enhanced membrane traffic invariably produces an accumulation of endocytic membranes around the Golgi apparatus, in which recycling endosomes concentrate. This peri-Golgi polarization has been documented by colocalization analysis of various membrane markers and applies also to active caspases associated with internalized receptor complexes. Hence, T lymphocytes show a diversion in the traffic of endocytic membranes after Fas stimulation that seems to resemble the polarization of membrane traffic after their activation.

Address correspondence to: Mauro Degli Esposti (mauro.esposti{at}manchester.ac.uk)

Abbreviations used: APC, allophycocyanin; HPA, Helix pomatia agglutinin; Rho-IETD-bis, rhodamine110carbonyl-Ile-Glu-Thr-Asp-bisamide; PE, phychoerythrin; RB, modified Ringer buffer; z-VAD, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone; WGA, wheat germ agglutinin.

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