Unconventional COPII-mediated secretory protein trafficking continues in the absence of the Sar1 GTPase

Coat protein complex II (COPII) plays an integral role in the packaging of secretory cargoes within membrane-enclosed transport carriers that leave the endoplasmic reticulum (ER) from discrete membrane subdomains. Lipid bilayer remodeling necessary for this process is driven initially by membrane penetration of the coat subunit Sar1 and further stabilized by assembly of a multi-layer complex of several COPII proteins. However, the relative contributions of these distinct factors to transport carrier formation and protein trafficking remain unclear. Here, we demonstrate that anterograde cargo transport from the ER continues in the absence of Sar1, although the unconventional carriers that form fail to efficiently deliver their contents to subsequent compartments in the secretory pathway. Instead, cargoes accumulate immediately adjacent to the perinuclear Golgi under these conditions, together with components of the COPII coat. Our findings highlight new mechanisms by which COPII promotes transport carrier biogenesis and strongly suggests that the Sar1 GTPase plays a critical role in transport carrier uncoating ahead of membrane fusion and secretory cargo delivery at acceptor compartments.