Crosstalk between Dpp and Tor signaling coordinates autophagy-dependent midgut degradation

Donna Denton,Shannon Nicolson,Sonia Dayan,Tianqi Xu,Sharad Kumar

doi:10.1038/s41419-019-1368-9

Abstract

The majority of developmentally programmed cell death (PCD) is mediated by caspase-dependent apoptosis; however, additional modalities, including autophagy-dependent cell death, have important spatiotemporally restricted functions. Autophagy involves the engulfment of cytoplasmic components in a double membrane vesicle for delivery to the lysosome. An established model for autophagy-dependent PCD is Drosophila larval midgut removal during metamorphosis. Our previous work demonstrated that growth arrest is required to initiate autophagy-dependent midgut degradation and Target of rapamycin (Tor) limits autophagy induction. In further studies, we uncovered a role for Decapentaplegic (Dpp) in coordinating midgut degradation. Here, we provide new data to show that Dpp interacts with Tor during midgut degradation. Inhibiting Tor rescued the block in midgut degradation due to Dpp signaling. We propose that Dpp is upstream of Tor and down-regulation promotes growth arrest and autophagy-dependent midgut degradation. These findings underscore a relationship between Dpp and Tor signaling in the regulation of cell growth and tissue removal.

Highlights

Programmed cell death (PCD) is essential for animal life and in most contexts is mediated by caspasedependent apoptosis[1]
The induction of autophagy occurs in response to upstream signaling pathways that converge on Target of rapamycin (TOR) kinase, as part of a multi-protein complex TORC110
To dissect out the regulatory mechanisms we identified dpp as a novel regulator of autophagy-dependent PCD16

Summary

Introduction

Programmed cell death (PCD) is essential for animal life and in most contexts is mediated by caspasedependent apoptosis[1]. Similar to Dpp, expression of TkvACT using NP1-GAL4 resulted in enlarged midguts and larval lethality (Fig. 1a). While the control midguts showed strong induction of autophagy as indicated by the presence of both red and yellow puncta, quenching of the GFP signal in the autolysosome, both Atg[1] knockdown and Dpp overexpression lacked any puncta (Fig. 1b).

Results

Conclusion