May 11, 2023
School of Biomedical Sciences is pleased to invite you to join the following seminar:
Date: 11 May 2023 (Thursday)
Time: 2:30 pm – 4:00 pm
Venue: Lecture Lecture Theatre 1, G/F, William M.W. Mong Block, 21 Sassoon Road
Speaker: Professor Vivek Malhotra, ICREA Research Professor and Group Leader, Coordinator of the Cell & Developmental Biology Program, Centre for Genomic Regulation (CRG)
Talk Title: TANGO1: from collagen secretion to controlling fibrosis
Professor Malhotra discovered a natural metabolite Ilimaquinone (IQ) that completely vesiculated the flat Golgi cisternae. IQ hyperactivates a fission machinery at the Golgi membranes that, we learnt for the first time, is functionally composed of a trimeric G‐protein, diacylglycerol and protein kinase D. Malhotra showed that cells use the same principle of membrane fission to produce transport carriers for exporting secretory proteins. This was the first demonstration of how vesicles of variable sizes are created without the function of coat proteins. In one of the first genome‐wide analysis in metazoans, Malhotra identified a large number of new genes that were required for transport and Golgi organization. These genes called TANGO include TANGO1, which is essential for assembling an export site at endoplasmic reticulum where it collects and tunnels bulky collagens and other big molecules to the next station of the secretory pathway. Malhotra identified mutations in TANGO1 that lead to collagenopathies thus validating the significance of his discoveries to physiology. Malhotra’s ongoing studies reveal that TANGO1 can be targeted to control tissue scarring and fibrosis. Malhotra showed that TANGO2 is required for fatty acid metabolism, which explain how defects in its function cause rhabdomyolysis, paroxysmal dystonia (https://tango2research.org). Malhotra identified new genes from another genome wide screen that explain how cells control the quantity and quality of mucins secreted and their link to human pathology such as the ulcerative colitis. Malhotra discovered genes that control how proteins, such as antioxidants and cytokines, that cannot enter the conventional ER‐Golgi pathway are secreted.
Our discovery of TANGO1, a ubiquitously expressed, ER-exit-site-resident, transmembrane protein has made the pathway of collagen secretion amenable to molecular analyses. TANGO1 acts as a scaffold to connect collagens in the lumen to COPII coats on the cytoplasmic side of ER. However, the growth of the collagen containing mega transport carrier is not simply by accretion of a larger COPII coated patch of ER membrane, but instead by rapid addition of premade ERGIC 53 containing small vesicles and tubules. This mode of transport carrier formation is fundamentally different from that used to produce small COPII vesicles. This allows transport of collagen from the lumen of ER to the next compartment of secretory pathway via transient tunnels. TANGO1 is genetically mutated in patients with collagenopathies and we can now target TANGO1 to control collagen hyper secretion dependent scarring and tissue fibrosis.
ALL ARE WELCOME
Should you have any enquiries, please feel free to contact Miss Angela Wong at 3917 9216.