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Membrane contact sites are critical junctures for organelle signaling and communication. Endoplasmic reticulum-plasma membrane (ER-PM) contact sites were the first membrane contact sites to be described; however, the protein composition and molecular function of these sites is still emerging. Here, we leverage yeast and Drosophila model systems to uncover a novel role for the Hobbit (Hob) proteins at ER-PM contact sites. We find that Hobbit localizes to ER-PM contact sites in both yeast cells and the Drosophila larval salivary glands, and this localization is mediated by an N-terminal ER membrane anchor and conserved C-terminal sequences. The C-terminus of Hobbit binds to plasma membrane phosphatidylinositols, and the distribution of these lipids is altered in hobbit mutant cells. Notably, the Hobbit protein is essential for viability in Drosophila, providing one of the first examples of a membrane contact site-localized lipid binding protein that is required for development. [ABSTRACT FROM AUTHOR]

Caspases perform critical functions in both living and dying cells; however, how caspases perform physiological functions without killing the cell remains unclear. Here we identify a novel physiological function of caspases at the cortex of Drosophila salivary glands. In living glands, activation of the initiator caspase dronc triggers cortical F-actin dismantling, enabling the glands to stretch as they accumulate secreted products in the lumen. We demonstrate that tango7, not the canonical Apaf-1-adaptor dark, regulates dronc activity at the cortex; in contrast, dark is required for cytoplasmic activity of dronc during salivary gland death. Therefore, tango7 and dark define distinct subcellular domains of caspase activity. Furthermore, tango7-dependent cortical dronc activity is initiated by a sublethal pulse of the inhibitor of apoptosis protein (IAP) antagonist reaper. Our results support a model in which biological outcomes of caspase activation are regulated by differential amplification of IAP antagonists, unique caspase adaptor proteins, and mutually exclusive subcellular domains of caspase activity. [ABSTRACT FROM AUTHOR]