Understanding Mammalian Golgi Trafficking Mechanisms

The long-term objective of this project is to elucidate the cellular and molecular mechanisms of a novel lipid- mediated pathway through the mammalian Golgi complex. The Golgi is responsible for the sorting, post- translational modification and trafficking of proteins and lipid to distinct locations in the cell. Alterations in Golgi structure and function are associated with cancer and neuropathology. Yet, how anterograde cargo traffics through the mammalian Golgi is a longstanding mystery that has been highly debated, with multiple models being proposed. Recent evidence indicates that palmitoylation in the early secretory pathway can act to sort proteins and to fast-track them through the Golgi, in parallel to slower trafficking of non-palmitoylated proteins. However, this concept begs the central questions of what the underlying machinery is, and of how it functions. New evidence indicates a role of TUG/ASPCR1 and associated tether and SNARE fusion components as key regulatory machinery. These targets and role of this pathway in Golgi structure and function will be characterized at the cellular level (Aim 1) and mechanistic level (Aim 2). The role of this pathway in trafficking physiologically important cargo (e.g. glucose transporters and G protein-coupled receptors) will be examined. Insight from these studies will decipher a novel ubiquitous mammalian pathway, help reconcile a major mystery in cell biology, and lead to new insights relevant in cancer and neurodegenerative disease. Project Number: 1R01GM164296-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: JONATHAN BOGAN | Institution: YALE UNIVERSITY, NEW HAVEN, CT | Award Amount: $605,140 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 CDB-S (90)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11337749