Activation of the cAMP/PKA signaling pathway is required for post-ecdysial cell death in wing epidermal cells of Drosophila melanogaster.
At the last step of metamorphosis in Drosophila, the wing epidermal cells are removed by programmed cell death during the wing spreading behavior after eclosion. The cell death was accompanied by DNA fragmentation demonstrated by the TUNEL assay. Transmission electron microscopy revealed that this cell death exhibited extensive vacuoles, indicative of autophagy. Ectopic expression of an anti-apoptotic gene, p35, inhibited the cell death, indicating the involvement of caspases. Neck ligation and hemolymph injection experiments demonstrated that the cell death is triggered by a hormonal factor secreted just after eclosion. The timing of the hormonal release implies that the hormone to trigger the death might be the insect tanning hormone, bursicon. This was supported by evidence that wing cell death was inhibited by a mutation of rickets, which encodes a G-protein coupled receptor in the glycoprotein hormone family that is a putative bursicon receptor. Furthermore, stimulation of components downstream of bursicon, such as a membrane permeant analog of cAMP, or ectopic expression of constitutively active forms of G proteins or PKA, induced precocious death. Conversely, cell death was inhibited in wing clones lacking G protein or PKA function. Thus, activation of the cAMP/PKA signaling pathway is required for transduction of the hormonal signal that induces wing epidermal cell death after eclosion.
Laboratory of Biology, Iwamizawa Campus, Hokkaido University of Education, Iwamizawa, Hokkaido 068-8642, Japan.
Ken-ichi
K
Kimura
Akitoshi
A
Kodama
Yosihiro
Y
Hayasaka
Takumi
T
Ohta
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D053938:DNA Fragmentation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000502:physiology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006458:Hemolymph / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007447:Invertebrate Hormones / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D018978:Molting / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*; D014921:Wings, Animal / Q000033:anatomy & histology / Q000378:metabolism
D029721:Drosophila Proteins; D007447:Invertebrate Hormones; D008164:Luminescent Proteins; D043562:Receptors, G-Protein-Coupled; D049452:Green Fluorescent Proteins; D015124:8-Bromo Cyclic Adenosine Monophosphate; C002295:bursicon; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019205:GTP-Binding Protein alpha Subunits, Gs