A Dimeric Sorting Code Medicates Cargo Selectivity by the COPII Coats

The flow of vesicles along the secretory pathway requires concerted actions among various regulators. The COPII complex, recruited by activated SAR1 GTPase on the endoplasmic reticulum, orchestrates protein interactions to enrich cargoes and generate transport vesicles en route to the Golgi. However, it remains challenging to investigate the highly dynamic interactions during the transport of COPII vesicles in cells. Here we developed a biochemical approach, based on the proximity-dependent labeling strategy, to capture the dynamics of COPII transport. When fused with a promiscuous biotin ligase Bir A, the fusion protein SAR1-Bir A marked the COPII machinery in a GTP-dependent manner. Interestingly, the cargo receptor LMAN1 undergoes a dynamic cycle of engaging-disengaging with the COPII coat. The selective packaging of LMAN1 into COPII vesicles requires a previously unrecognized dimeric sorting code, generated by oligomerization of the cargo receptor. Similar oligomerization events have been observed with ot...The flow of vesicles along the secretory pathway requires concerted actions among various regulators. The COPII complex, recruited by activated SAR1 GTPase on the endoplasmic reticulum, orchestrates protein interactions to enrich cargoes and generate transport vesicles en route to the Golgi. However, it remains challenging to investigate the highly dynamic interactions during the transport of COPII vesicles in cells. Here we developed a biochemical approach, based on the proximity-dependent labeling strate中国生物物理学会、中国生化与分子生物学学会、中国细胞生物学会