Department of Cell Biology, Yale School of Medicine, New Haven, United States; Laboratoire de Physique de l’Ecole normale supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université de Paris, Paris, France
Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain
We have previously shown TANGO1 organises membranes at the interface of the endoplasmic reticulum (ER) and ERGIC/Golgi (Raote et al., 2018). TANGO1 corrals retrograde membranes at ER exit sites to create an export conduit. Here the retrograde membrane is, in itself, an anterograde carrier. This mode of forward transport necessitates a mechanism to prevent membrane mixing between ER and the retrograde membrane. TANGO1 has an unusual membrane helix organisation, composed of one membrane-spanning helix (TM) and another that penetrates the inner leaflet (IM). We have reconstituted these membrane helices in model membranes and shown that TM and IM together reduce the flow of lipids at a region of defined shape. We have also shown that the helices align TANGO1 around an ER exit site. We suggest this is a mechanism to prevent membrane mixing during TANGO1-mediated transfer of bulky secretory cargos from the ER to the ERGIC/Golgi via a tunnel.
