Functional analysis of a family of TANGO1-like proteins. What is the influence on transport of large cargos and are so-called megacarriers generated?
Final Report Abstract
During the DFG Research Fellowship the applicant was able to show that cultured human cell lines express a range of TANGO1 like proteins, that mostly localize to the ER exit sites were they might play a role regulating secretion. We have shown that two of the family members TANGO1spliced and cTAGE5 interact in cells and that the expression of both is needed for the export of a subset of cargo proteins but not for general secretion. We were then looking for interaction partners for TANGO1 that would also affect the secretion of Collagen VII but not the secretion of general cargo. And we have identified two proteins, SLY1 and Syntaxin 18 that fit this description. These proteins work on the cytosolic side at the level of the ER. By careful analysis we could show that the depletion of SLY1 affects neither the targeting of TANGO1 to Collagen VII and ER exit sites nor the formation of functional exit sites. And that SLY1 and Syntaxin 18 like TANGO1 are not required for the secretion of Collagen I. The fact that both Syntaxin 18 and SLY1 are part of the vesicle fusion machinery at the ER led us to propose a model were the generation of a Collagen VII transport carrier needs a fusion step. But there is also the possibility that Collagen VII is directly shuttled to next secretory compartment by directly fusing the two membranes.
Publications
- SLY1 and Syntaxin 18 specify a distinct pathway for Procollagen VII export from the endoplasmic reticulum. elife. 2014 May 19;3:e02784
Nogueira C, Erlmann P, Villeneuve J, Santos AJ, Martínez- Alonso E, Martínez-Menárguez JÁ, Malhotra V
(See online at https://doi.org/10.7554/eLife.02784)
