The Golgi complex is a ubiquitous eukaryotic organelle that plays a central role in post-translational processing and sorting of newly synthesized proteins and lipids. Both of these functions of the Golgi complex are critical, since defects in processing and targeting can lead to disease. In mammalian cells, the Golgi complex has an unusual structure consisting of sets of stacked cisternal membranes gathered into a ribbon near the nucleus. The function of this elaborate structure is unknown, but it may contribute to efficient processing and sorting of cargo. Golgi structure can be rapidly and reversibly altered during passage of cargo. The structural alterations are particularly dramatic during transport of large cargo such as lipoprotein particles, procollagen bundles, and enveloped viruses that bud into intracellular compartments. The mechanism by which the Golgi complex undergoes reversible morphological changes to accommodate large cargo has not been experimentally addressed. The proposed experiments will test the hypothesis that arrival of large cargo at the Golgi activates signaling pathways that result in cisternal dilation and efficient intra-Golgi transport.
The specific aims of the project are to: (1) determine how the Golgi is modified to accommodate and transport large enveloped virus particles, using coronavirus as a model; and (2) compare and contrast the mechanism used by chylomicrons produced by intestinal epithelial cells as well as a synthetic large cargo that can be staged at various points in the secretory pathway. These studies will provide novel information on unstudied aspects of Golgi structure and function, and lead to insights into normal cellular processes that are disrupted in disease.
The Golgi complex is a ubiquitous cellular organelle that is instrumental in secretion of cargo; defects in this process lead to disease. The proposed experiments will increase our understanding of how the Golgi complex structure must be altered to accommodate secretion of large cargo, including lipoprotein particles and enveloped viruses. These studies will lead to new approaches to combat human diseases, including virus infections and obesity.
