There has been a rather large hole in our understanding of how the endoplasmic reticulum (ER), the cell’s protein and lipid assembly plant, manages to export very large molecules. A whole array of important but bulky proteins are simply too big to be exported inside COPII-coated vesicles, the ER’s favorite shipping containers for cargoes on their way to the Golgi apparatus. The big guys, the precursor molecules of collagen, chylomicrons, and very low-density lipoproteins (VLDLs), are just too large for the COPII-vesicles that pack up the majority of newly minted proteins emerging at ER exit sites.
Yet these big proteins are important. António J.M. Santos and ASCB member Vivek Malhotra at the Barcelona Institute of Science and Technology point out that “Collagens are the most abundant of the secretory proteins, as they constitute ∼25% of our dry body weight and are essential for tissue organization and function.” Somehow collagen and the other big guys do make their exit from the ER and now Santos and Malhotra plus colleagues at Barcelona’s Universitat Pompeu Fabra have fresh evidence of how they do it—they tango. The Malhotra lab had already shown that a transmembrane receptor protein they named TANGO1 is necessary for the successful export of procollagen from the ER, but in their new JCB paper, the researchers take it a step further with the discovery of a new chimeric protein they are calling TANGO1-like (TALI). TANGO1 binds TALI and together they bind apolipoprotein B to pack up chylomicrons and VLDLs. For collagens, though, the researchers says that it takes only TANGO1 to tango at the ER exit. A commentary on the paper by former ASCB president and Stanford professor Susanne Pfeffer is here.
