CD45-mediated fodrin cleavage during galectin-1 T cell death promotes phagocytic clearance of dying cells.
Disassembly and phagocytic removal of dying cells is critical to maintain immune homeostasis. The factors that regulate fragmentation and uptake of dying lymphocytes are not well understood. Degradation of fodrin, a cytoskeletal linker molecule that attaches CD45 to the actin cytoskeleton, has been described in apoptotic cells, although no specific initiator of fodrin degradation has been identified. CD45 is a glycoprotein receptor for galectin-1, an endogenous lectin that can trigger lymphocyte apoptosis, although CD45 is not required for phosphatidylserine externalization or DNA degradation during galectin-1 death. In this study, we show that fodrin degradation occurs during galectin-1 T cell death and that CD45 is essential for fodrin degradation to occur. In the absence of CD45, or if fodrin degradation is prevented, galectin-1-induced cell death is not accompanied by membrane blebbing, although phosphatidylserine externalization and DNA degradation proceed, indicating that fodrin degradation occurs via a distinct pathway compared with the pathway that leads to these other hallmarks of cell death. Moreover, there is slower phagocytic uptake by macrophages of T cells in which fodrin degradation is prevented, relative to T cells in which CD45-mediated fodrin degradation occurs. These studies identify a novel role for CD45 in regulating cellular disassembly and promoting phagocytic clearance during galectin-1-induced T cell death.
Pang
Mabel
M
Department of Pathology and Laboratory Medicine, University of California Los Angeles School of Medicine, Los Angeles, CA 90095, USA.
He
Jiale
J
Johnson
Pauline
P
Baum
Linda G
LG
D017209:Apoptosis / Q000276:immunology*; D002352:Carrier Proteins / Q000378:metabolism*; D037483:Galectin 1 / Q000502:physiology*; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D008840:Microfilament Proteins / Q000378:metabolism*; D010587:Phagocytosis; D013601:T-Lymphocytes / Q000166:cytology*; D013049:Spectrin
D002352:Carrier Proteins; D037483:Galectin 1; D017493:Leukocyte Common Antigens; D008840:Microfilament Proteins; D013049:Spectrin