The Sar1 GTPase coordinates biosynthetic cargo selection with endoplasmic reticulum export site assembly

Cargo selection and export from the endoplasmic reticulum is mediated by the COPII coat machinery that includes the small GTPase Sari and the Sec23/24 and Sec13/31 complexes. We have analyzed the sequential events regulated by purified Sari and COPII coat complexes during synchronized export of cargo from the ER in vitro. We find that activation of Sari alone, in the absence of other cytosolic components, leads to the formation of ER-derived tubular domains that resemble ER transitional elements that initiate cargo selection, These Sari-generated tubulardomains were shown to be transient, functional intermediates in ER to Golgi transport in vitro. By following cargo export in live cells, we show that ER export in vivo is also characterized by the formation of dynamic tubular structures. Our results demonstrate an unanticipated and novel role for Sari in linking cargo selection with ER morphogenesis through the generation of transitional tubular ER export sites.