Fig. 2.

Proposed role of TANGO1 and cTAGE5. (1) cTAGE5 binds Sec12 and concentrates it to the ERES. TANGO1 binds Hsp47 through its ER-luminal SH3-domain, directing procollagen to ERES. (2) Efficient Sar1–GTP/GDP cycling is facilitated by sedlin and Sec12. The COPII prebudding complex is further regulated by TANGO1 together with cTAGE5 that bind to the COPII inner layer. The NRZ tethering complex is recruited by TANGO1/cTAGE5 and recruits ERGIC membranes to the forming COPII complex. TANGO1/cTAGE5 assemble the fusion machinery SLY1 and syntaxin18 that drive incorporation of ERGIC membranes into the vesicle to allow procollagen incorporation into the carrier (3). Some uncertainty remains as to the precise structure of procollagen trimers on exit from the ER such that larger COPII-coated carriers might not be necessary