CD95, Fas receptor

Author: V. Dimov, M.D., Fellow, Creighton University Division of Allergy & Immunology
Reviewer: S. Randhawa, M.D., Fellow, LSU (Shreveport) Department of Allergy & Immunology

CD95 is a Fas Receptor, a receptor for Fas ligand (CD178), an extrinsic apoptotic signal.

The Fas receptor (FasR) is the most intensely studied death receptor. Its aliases include CD95, Apo-1, and tumor necrosis factor receptor superfamily, member 6 (TNFRSf6). The gene is situated on chromosome 10 in humans.

CD95 (Fas) causes apoptosis when ligated by FasL. CD178 is Fas ligand. CD178 (FasL) binds CD95 (Fas) and causes apoptosis. CD95 (Fas) is defective in ALPS.


Fas death domain (TNF receptor superfamily, member 6). Image source: Wikipedia, public domain.


This video describes the process by which apoptosis is activated by T cells. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.

Fas forms the death inducing signalling complex (DISC) upon ligand binding.

After death domain (DD) aggregation, the receptor complex is internalized via the cellular endosomal machinery. This allows the adaptor molecule FADD to bind the death domain of Fas.

FADD also contains a death effector domain (DED) near its amino terminus, which facilitates binding to the DED of FADD-like ICE (FLICE), more commonly referred to as caspase-8.

Active caspase-8 is then released from the DISC into the cytosol, where it cleaves other effector caspases, eventually leading to DNA degradation, membrane blebbing, and other hallmarks of apoptosis.

The death-inducing signaling complex or DISC is a multi-protein complex formed by members of the death receptor family of apoptosis-inducing cellular receptors. The typical example is FasR, which forms the DISC upon trimerization as a result of its ligand (FasL) binding.

DISC is composed of the death receptor, FADD, and caspase 8. It transduces a downstream signal cascade resulting in apoptosis.


Death-inducing signaling complex. Image source: Wikipedia, public domain.


T Cell Killing. This video describes the actions of cytotoxic T cells. This video is from: Janeway's Immunobiology, 7th Edition, Murphy, Travers, & Walport. Source: Garland Science.


Apoptosis. This video describes the process of apoptosis, or programmed cell death. This video is from: Janeway's Immunobiology, 7th Edition, Murphy, Travers, & Walport. Source: Garland Science.

References

Fas receptor, Wikipedia, the free encyclopedia.
Death-inducing signaling complex. Wikipedia, the free encyclopedia.

Published: 12/15/2008
Updated: 06/19/2010

No comments: