Collection From Molecules and Cells to Human Health : Ideas and concepts
Organizer(s)
Date(s)
27/04/2024
Building a machine at endoplasmic reticulum for collagen export
Secreted collagens compose 25% of our dry body weight and necessary for tissue organization, and skin and bone formation. But how are these bulky cargoes that are too big to fit into a conventional COPII vesicle exported from the ER? Our discovery of TANGO1 (Bard, Nature 2006; Saito, Cell 2009; Saito, Mol Biol Cell 2011; Santos, J Cell Biol 2016; Malhotra, Ann Rev Cell Dev Biol 2019), a ubiquitously expressed, ER-exit-site-resident, transmembrane protein has made the pathway of collagen secretion amenable to molecular analysis. 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 small vesicles. This mode of transport carrier formation is fundamentally different from that used to produce small COPII vesicles. We have seen that TANGO1 rings the ER exit site and thus organizies a sub compartment within the ER (Nogueira, eLife 2014; Santos, eLife 2015; Raote, J Cell Biol 2017). We have now mapped all the components that work in concert along with the cargo to assemble TANGO1 into a ring (Raote et al., 2018. In review). Mathematical modelling, biochemistry and super resolution microscopy based analyses of this process will be discussed. TANGO1-family proteins (cyan) assembly into a ring at an ERES is mediated by interactions 1. with COPII (orange) 2. with triple helical collagen (purple), 3. amongst the TANGO1 family proteins 4. with the NRZ tether (dark blue) which links TANGO1 to ERGIC membranes. TANGO1 acts as a lineactant, delaying the binding of the outer COPII coat and allowing for the formation of a mega-carrier.
