Procollagens, pre-chylomicrons, and pre–very low-density lipoproteins (pre-VLDLs) are too big to fit into conventional COPII-coated vesicles, so how are these bulky cargoes exported from the endoplasmic reticulum (ER)? We have shown that TANGO1 located at the ER exit site is necessary for procollagen export. We report a role for TANGO1 and TANGO1-like (TALI), a chimeric protein resulting from fusion of MIA2 and cTAGE5 gene products, in the export of pre-chylomicrons and pre-VLDLs from the ER. TANGO1 binds TALI, and both interact with apolipoprotein B (ApoB) and are necessary for the recruitment of ApoB-containing lipid particles to ER exit sites for their subsequent export. Although export of ApoB requires the function of both TANGO1 and TALI, the export of procollagen XII by the same cells requires only TANGO1. These findings reveal a general role for TANGO1 in the export of bulky cargoes from the ER and identify a specific requirement for TALI in assisting TANGO1 to export bulky lipid particles.

We acknowledge support of the Ministerio de Economía y Competitividad, “Centro de Excelencia Severo Ochoa 2013-2017,” SEV-2012-0208. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement 625149 to A.J.M. Santos and European Research Council grant agreement 268692 to V. Malhotra. This work reflects only the author’s views, and the community is not liable for any use that may be made of the information contained therein. V. Malhotra is an Institució Catalana de Recerca i Estudis Avançats professor at the Center for Genomic Regulation, and the work in his laboratory is funded by grants from Ministerio de Economía y Competitividad’s Plan Nacional (ref. BFU2013-44188-P) and Consolider (CSD2009-00016).