Ubiquitin-dependent regulation of COPII coat size and function

Packaging of proteins from the ER into COPII-vesicles is essential for secretion. In cells, most COPII-vesicles are ~60-80nm in diameter, yet some must increase their size to accommodate 300-400nm procollagen fibers or chylomicrons. Impaired COPII function results in collagen deposition defects, cranio-lenticulo-sutural dysplasia, or chylomicron retention disease, but mechanisms to enlarge COPII-coats have remained elusive. Here, we have identified the ubiquitin ligase Cul3(Klhl12) as a regulator of COPII coat formation. Cul3(Klhl12) catalyzes the monoubiquitination of the COPII-component Sec31 and drives the assembly of large COPII coats. As a result, ubiquitination by Cul3(Klhl12) is essential for collagen export, yet less important for the transport of small cargo. We conclude that monoubiquitination controls the size and function of a vesicle coat.