BmCaspase‐8‐like regulates autophagy by suppressing BmDREDD‐mediated cleavage of BmATG6

Abstract

Autophagy plays an important role in tissue remodeling during insect development. The interplay between autophagy‐related (ATG) proteins and caspases regulates the autophagic activity of ATGs, thereby modulating the process of autophagy. Our previous study characterized BmCaspase‐8‐like (BmCasp8L) as a caspase suppressor that inhibits apoptosis and immune signaling by suppressing the activation of death‐related ced‐3/Nedd2‐like caspase (DREDD), a caspase‐8 homolog in silkworm. In this study, we explored the regulatory role of BmCasp8L in autophagy. We found that the expression of Bmcasp8l increased from the late spinning stage to the pupa stage in the posterior silk gland (PSG), correlating with the expression patterns of Bmatg8 and Bmatg6. RNA interference‐mediated downregulation of BmCasp8L expression significantly decreased starvation‐induced autophagic influx as determined by the levels of BmATG8–phosphatidylethanolamine and the percentage of cells displaying punctate enhanced green fluorescent protein‐BmATG8. Conversely, the overexpression of BmCasp8L significantly increased autophagic influx. We also found that BmCasp8L underwent autophagic degradation induced by starvation and that it was colocalized with BmATG8. Lastly, we demonstrated that BmDREDD attenuated autophagy and BmCasp8L suppressed BmDREDD‐mediated cleavage of BmATG6. Taken together, our results demonstrated that BmCasp8L is a novel proautophagic molecule which suppresses BmDREDD‐mediated cleavage of BmATG6 and is a target for autophagy.

Cloning, Characterization and Functional Analysis of Caspase 8-like Gene in Apoptosis of Crassostrea hongkongensis Response to Hyper-Salinity Stress

“…The Caspase-8-like gene, which is the most similar to caspase 8, is considered to function as an initiator caspase and plays crucial roles in extrinsic apoptotic pathways in some mollusk species [4,8]. However, some researchers found that caspase-8-like worked as a caspase suppressor to inhibit apoptosis and immune signaling in silkworm (Bombyx mori) [9]. The contradiction in this research implies that functional differences in caspase-8-like exist in different invertebrates.…”