Abstract
TANGO1 binds and exports Procollagen VII from the endoplasmic reticulum (ER). In this study, we report a connection between the cytoplasmic domain of TANGO1 and SLY1, a protein that is required for membrane fusion. Knockdown of SLY1 by siRNA arrested Procollagen VII in the ER without affecting the recruitment of COPII components, general protein secretion, and retrograde transport of the KDEL-containing protein BIP, and ERGIC53. SLY1 is known to interact with the ER-specific SNARE proteins Syntaxin 17 and 18, however only Syntaxin 18 was required for Procollagen VII export. Neither SLY1 nor Syntaxin 18 was required for the export of the equally bulky Procollagen I from the ER. Altogether, these findings reveal the sorting of bulky collagen family members by TANGO1 at the ER and highlight the existence of different export pathways for secretory cargoes one of which is mediated by the specific SNARE complex containing SLY1 and Syntaxin 18.DOI: http://dx.doi.org/10.7554/eLife.02784.001.
Highlights
Collagens are the most abundant secretory proteins, comprising 25–30% of the human body dry weight (Pataridis et al, 2008)
We describe in this study, our data that reveal the existence of different export routes for secretory cargoes from the endoplasmic reticulum (ER): of specific interest is the finding that SLY1 and the ER specific t-SNARE Syntaxin 18 (STX18) are necessary for the export of PC VII but not of the bulky PC I from the ER
Of interest was the finding of SLY1 in the pool of proteins cross-linked to TANGO1
Summary
Collagens are the most abundant secretory proteins, comprising 25–30% of the human body dry weight (Pataridis et al, 2008) They are required for cell attachment, tissue organization and remodeling, and for the differentiation of chondrocytes to produce mineralized bones (Gelse et al, 2003; Wilson et al, 2011). There are at least 28 different kinds of collagens, composed of homo or hetero trimers of polypeptide chains coiled around each other to form a triple helix (Shoulders and Raines, 2009) These unbendable triple helices, which can be up to 450 nm long, as in the case of Collagen VII, are too big to fit into the conventional transport carriers of the secretory pathway that have been identified far (Malhotra and Erlmann, 2011).
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call