Compartmentalization of Fas and Fas ligand may prevent auto- or paracrine apoptosis in epithelial cells.
Oligomerization of Fas receptor by its ligand, FasL, activates a signaling cascade that leads to apoptosis of Fas bearing cells. Interestingly, many epithelia coexpress Fas and FasL, yet FasL does not trigger Fas present on the same or neighboring cells to induce spontaneous apoptosis. Here, we show that Fas and FasL are segregated from each other to different cellular compartments in kidney epithelial MDCK cells. While Fas is restricted to the basolateral surface, FasL is sequestered to an intracellular compartment and, a lesser extent, the apical surface. This spatial segregation of Fas and FasL may explain how epithelial cells can constitutively express a functional Fas pathway but avoid auto- or paracrine cell death. Compromising this spatial segregation in physiological or pathological situations may play a so far underestimated role in initiating apoptosis of epithelial cells.
Tan
Kok Hwee
KH
Institute of Molecular and Cell Biology, Epithelial Cell Biology Laboratory, 30 Medical Drive, Singapore 117609, Singapore.
Hunziker
Walter
W
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019898:Autocrine Communication / Q000502:physiology*; D002451:Cell Compartmentation / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism*; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D019899:Paracrine Communication / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism*
D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor