C. elegans is used to unravel the complex signalling processes that control apoptosis and cell corpse engulfment. Apoptosis is partly directed by a pathway using CED-3/Caspase and CED-4/Apaf1 while the distinct process of corpse engulfment is mediated by pathways that include: (i) CED-1/SREC, CED-6/GULP, CED-7/ABC1, DYN-1/Dynamin and (ii) CED-2/CrkII, CED-5/DOCK180, CED-10/RAC, CED-12/ELMO and (iii) ABI-1/ABI and ABL-1/ABL. UNC-53/Nav2 is a cytoskeletal binding protein that controls cell migration and interacts with ABI-1 and UNC-73/TRIO. UNC-53 is homologous to the Neuron Navigator (Nav) genes, a gene family with diverse functions, including the growth and development of tumorigenic cells. To study a potential role for UNC-53 in cell death processes we first compared the number of residual cell corpses in the pharynxes of newly hatched L1 single mutants of
ced-1,
ced-2,
ced-5, and
ced-10 to corresponding double mutants with
unc-53.
unc-53 loss suppressed cell corpse engulfment of
ced-1,
ced-2, and
ced-10 but not
ced-5 mutants, placing
unc-53 outside of a
ced-1 pathway but not independent of
ced-2 and
ced-5.
unc-53 suppressed the distal tip cell guidance defects frequently observed in these mutants and had a striking effect on
ced-10 and
mig-2/RHO animals, reducing the frequency of anteroposterior polarity reversals.
unc-53 loss also increased the amount of CED-10 as measured by increased GFP in
unc-53 (
n152); CED-10::GFP strains compared to animals carrying the CED-10::GFP integrated array alone. We next used time-lapse microscopy to see if
unc-53 affected the timing, number or morphology of cell corpses. Morphology and timing were normal in
unc-53, but we found that
unc-53 (
n152) null mutants had significantly fewer apoptotic corpses from the comma stage through to the 3-fold stage of embryogenesis. This latter observation suggests that
unc-53 may influence cell apoptosis directly. We next tested for a role for
unc-53 (
n152) in the apoptosis of neuronal cells.
unc-53 (
n152) enhanced the weak allele
ced-3 (
n2427) and blocked neuronal cell death in cells normally fated to die (P2.aap, P9-12.aap).
unc-53 (
n152) also significantly blocks CED-3 and CED-4 mediated killing when these proteins are ectopically expressed in the mechanosensory neurons. Our experiments suggest that
unc-53 impacts cell death directly through a pathway involving CED-3/CED-4 but may have an additional role in cell corpse engulfment.