Regulation of cell number by MAPK-dependent control of apoptosis: a mechanism for trophic survival signaling.
Trophic mechanisms in which neighboring cells mutually control their survival by secreting extracellular factors play an important role in determining cell number. However, how trophic signaling suppresses cell death is still poorly understood. We now show that the survival of a subset of midline glia cells in Drosophila depends upon direct suppression of the proapoptotic protein HID via the EGF receptor/RAS/MAPK pathway. The TGFalpha-like ligand SPITZ is activated in the neurons, and glial cells compete for limited amounts of secreted SPITZ to survive. In midline glia that fail to activate the EGFR pathway, HID induces apoptosis by blocking a caspase inhibitor, Diap1. Therefore, a direct pathway linking a specific extracellular survival factor with a caspase-based death program has been established.
Bergmann
Andreas
A
Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Tugentman
Michael
M
Shilo
Ben Zion
BZ
Steller
Hermann
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004330:Drosophila / Q000166:cytology* / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D018631:ras Proteins / Q000378:metabolism
D061945:Caspase Inhibitors; C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; C076026:spi protein, Drosophila; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases; D018631:ras Proteins