Multi-user equipment approved in grant 23/04532-9: refrigerated benchtop centrifuge

Abstract

The emergence of life diversity and complexity has been facilitated by intercellular communication, which is partially supported by a highly conserved pathway known as the conventional secretory pathway. This pathway involves the secretion of proteins containing a signal peptide through the endoplasmic reticulum-Golgi apparatus-final destination route. Although some questions remain open, its basic machinery has been well-described. Until recently, it was believed that this exocytic route was the sole pathway used by the cell to export a wide range of cargo proteins. However, additional pathways have also been revealed to secrete proteins lacking a signal sequence. These findings challenged the current understanding of a single secretory pathway and have led to exploring alternative routes dedicated to secretion, termed unconventional protein secretion (UPS). Although UPS is becoming increasingly important for cellular adaptation to stress, many crucial aspects of its regulation and biological function are poorly understood. A family of Golgi-resident proteins, the Golgi Reassembly and Stacking Proteins (GRASPs), plays a pivotal role in two of the UPS types described so far. GRASPs are key pillars of this proposal, which irradiates from them to address five different and interconnected aspects of UPS: (1) GRASPs in different organisms; (2) GRASP partners; (3) GRASP and their partner's interactions with membranes; (4) supramolecular arrangments of GRASPs and their partners; (5) in cell studies. This thematic grant proposal intends to bridge the gap between the molecular and cellular worlds by starting from the molecular biophysics of GRASPs and walking along the pathway leading to the cellular implications of what is observed in the test tube. Such a strategy has the potential to yield a better understanding of the fundamental aspects of UPS, with a high impact on cell homeostasis and communication and their disease-related malfunctions. (AU)