Developmentally-regulated post-apocrine cell death of Drosophila salivary glands utilizes ER stress-linked apoptosis

Abstract

The Drosophila salivary glands (SGs) are highly specialized secretory organs that provide an ideal model to study developmentally-associated programmed cell death (PCD), as they respond to the steroid hormone ecdysone to undergo programmed histolysis during larval-to-adult metamorphosis. Understanding the mechanism underlying PCD is a prerequisite to investigating how its timing is coordinated with a massive apocrine secretion that concludes just hours earlier. Here we show that SG apoptosis is linked to endoplasmic reticulum (ER) disintegration via an ER-stress mechanism. Depletion of ER calcium stores was very effective at inducing ER vesiculation and subsequent cell death. Depletion led to the activation of Xbp1, implicating the involvement of unfolded protein response (UPR) signaling. Genetic manipulation of ER-resident proteins, chaperones and co-chaperones resulted in a widespread and fast vesiculation of the ER, typical of that seen during the final apoptotic stage in wild type animals. In contrast, the genetic removal of the SERCA pump prevented SG apoptosis. Being the largest organelle in the SG, the ER is able to provide for a robust and extremely fast spread of cell-death signals. Since malfunction of any of the mentioned proteins led to a fast apoptotic response, either each can function as sensor of an ER apoptotic pathway, or their action converges onto a common sensor to provide a universal signal to initiate a cascade leading to rapid caspase activation and ER vesiculation.