The CD44 standard/ezrin complex regulates Fas-mediated apoptosis in Jurkat cells.
The transmembrane receptor CD44 conveys important signals from the extracellular microenvironment to the cytoplasm, a phenomena known as "outside-in" signaling. CD44 exists as several isoforms that result from alternative splicing, which differ only in the extracellular domain but yet exhibit different activities. CD44 is a binding partner for the membrane-cytoskeleton cross-linker protein ezrin. In this study, we demonstrate that only CD44 standard (CD44s) colocalizes and interacts with the actin cross-linkers ezrin and moesin using well-characterized cell lines engineered to express different CD44 isoforms. Importantly, we also show that the association CD44s-ezrin-actin is an important modulator of Fas-mediated apoptosis. The results highlight a mechanism by which signals from the extracellular milieu regulate intracellular signaling activities involved in programmed cell death.
Mielgo
Ainhoa
A
Institute of Medical Microbiology, Department of Clinical and Biological Sciences, University of Basel, Petersplatz 10, 4003 Basel, Switzerland.
Brondani
Vincent
V
Landmann
Lukas
L
Glaser-Ruhm
Andrea
A
Erb
Peter
P
Stupack
Dwayne
D
Günthert
Ursula
U
D000199:Actins / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism / Q000502:physiology*; D006041:Goats; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism / Q000502:physiology*; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000378:metabolism*; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism / Q000502:physiology; D019014:fas Receptor / Q000502:physiology*; D000099149:Ezrin
D000199:Actins; D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D046912:Multiprotein Complexes; D019014:fas Receptor; D000099149:Ezrin; C491901:FAS protein, human