Affiliation: Stanford University School of Medicine
Keywords: t. cell junctions and adhesion; a. caspases
The adult Drosophila midgut shrinks as a result of nutrient deprivation. Shrinkage is in part due to reduction in enterocyte cell volume and cell loss by enterocyte cell extrusion - there was two-fold increase in extrusions upon fasting. At steady-state most cells activated executioner caspases before they extruded. Inhibition of caspase activation blocked extrusions at steady-state. However, in fasted guts, ~70% of extruded cells were negative for cleaved caspase. TOR signaling is a conserved pathway that senses and responds to nutrient signals. Paradoxically, TOR signaling activation by inhibiting Tsc2 or Rheb overexpression increased cell extrusions in the midgut. Tsc2 inhibition showed dramatic resistance to fasting compared to control flies, while flies with blocked caspase activation had significantly shorter lifespans. Further studies can help understand the role of TOR signaling in mediating extrusions to achieve organ shrinkage in the adult Drosophila midgut.