Tumor necrosis factor-related apoptosis-inducing ligand 1 (TRAIL1) enhances the transition of red blood cells from the larval to adult type during metamorphosis in Xenopus.
The transition of red blood cells (RBCs) from primitive to definitive erythropoiesis is conserved across vertebrates. In anuran amphibians, the larval RBCs from primitive erythropoiesis are replaced by adult RBCs from definitive erythropoiesis during metamorphosis. The molecular mechanisms by which the primitive (larval) blood cells are specifically removed from circulation are not yet understood. In this study, we identified Xenopus tumor necrosis factor-related apoptosis-inducing ligand 1 (xTRAIL1) and xTRAIL2 as ligands of Xenopus death receptor-Ms (xDR-Ms) and investigated whether TRAIL signaling could be involved in this transition. The Trail and xDR-M genes were highly expressed in the liver and RBCs, respectively, during metamorphosis. Interestingly, xTRAIL1 enhanced the transition of the RBCs, and a dominant-negative form of the xTRAIL1 receptor attenuated it, when injected into tadpoles. Moreover, xTRAIL1 induced apoptosis in larval RBCs, but had little effect on adult RBCs in vitro. We also found that adult RBCs treated with staurosporine, a protein kinase C (PKC) inhibitor, were sensitized to xTRAIL1. The mRNAs for PKC isoforms were up-regulated in RBCs during metamorphosis. These results suggest that xTRAIL1 can cause apoptosis, probably mediated through xDR-Ms, in larval RBCs, but may not kill adult RBCs, presumably owing to PKC activation, as part of the mechanism for RBC switching.
Tamura
Kei
K
Department of Biosciences, School of Science, Kitasato University, Sagamihara, Japan.
Mawaribuchi
Shuuji
S
Yoshimoto
Shin
S
Shiba
Tadayoshi
T
Takamatsu
Nobuhiko
N
Ito
Michihiko
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D004912:Erythrocytes / Q000166:cytology* / Q000502:physiology; D007668:Kidney / Q000166:cytology; D008675:Metamorphosis, Biological / Q000502:physiology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection; D029867:Xenopus Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014982:Xenopus laevis / Q000235:genetics* / Q000254:growth & development
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C547658:TNFSF10 protein, Xenopus; D029867:Xenopus Proteins; C484516:death receptor M1, Xenopus; C484517:death receptor M2, Xenopus; C547659:tnfsf10l protein, Xenopus; D011493:Protein Kinase C; D053148:Caspase 3