Drosophila NMNAT Maintains Neural Integrity Independent of Its NAD Synthesis Activity
Figure 9
Overexpression of Enzymatically Active or Inactive NMNAT Can Rescue the Neurodegeneration Phenotype Caused by rdgA, trpP365, and Constant Light Exposure
(A–D) Ommatidial morphology of rdgA mutant retinae (A) expressing wild-type NMNAT (B) or enzymatically inactive NMNAT (C) at 2 d of age. The quantification of the number of rhabdomeres per ommatidium (blue columns) and the size of vacuoles per surface area (red columns) are displayed (D). The number of rhabdomeres per ommatidium is significantly rescued by expression of wild-type or enzymatically inactive NMNAT. The vacuole size is significantly reduced with the expression of inactive NMNAT but not wild-type NMNAT.
(E–H) Ommatidial morphology of trpP365 mutant retinae (E) expressing wild-type NMNAT (F) or enzymatically inactive NMNAT (G) at 2 d of age. The quantification of the number of rhabdomeres per ommatidium (blue columns) and the size of vacuoles per surface area (red columns) are displayed in (H). The number of rhabdomeres per ommatidium is significantly rescued by expressing enzymatically active or inactive NMNAT, although the vacuole size remains unchanged.
(I–M) Ommatidial morphology of 30-d-old wild-type flies either kept under ambient light in a 12-h light/dark cycle (I), or under constant intense light (2.2 kLux) (J–L). Overexpression of wild-type NMNAT (K) and the inactive protein NMNAT-WR (L) significantly protect ommatidial morphology compared to wild type (J). Quantification (M) shows an increased number of rhabdomeres per ommatidium (blue columns) and a reduction in vacuole size (red columns). Five animals per genotype and 400 μm2 of ommatidia per animal were quantified. A single asterisk (*) indicates p < 0.05; double asterisks (**) indicate p < 0.005; and triple asterisks (***) indicate p < 0.0005 (Student t-test).