Palade's corpus placed small vesicles as the sole means to transport proteins across stable distinct compartments of the secretory pathway. We suggest that cargo, spatial organization of secretory compartments, and the timing of fission of cargo-filled containers dictate the design of transport intermediates that can be vesicles and transient direct tunnels.

We acknowledge support from the Spanish Ministry of Economy and Competitiveness through the Program “Centro de Excelencia Severo Ochoa 2013-2017” (SEV-2012-0208), support from the CERCA Program/Generalitat de Catalunya and fellowship IJCI-2017-34751 (to I. Raote). V. Malhotra is an Institució Catalana de Recerca i Estudis Avançats professor at the Centre for Genomic Regulation and the work in his laboratory is funded by grants from MINECO’s Plan Nacional (BFU2013-44188-P) and Consolider (CSD2009-00016). The project has received research funding from the European Union. This paper reflects only the authors’ views. The European Union is not liable for any use that may be made of the information contained therein.