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Pantazopoulou, A.

Publications and source records attributed to Pantazopoulou, A..

3 recordsLinked to original sources

The AP-1 clathrin adaptor has a conserved role in recycling resident proteins of the trans-Golgi network

Although the AP-1 clathrin adaptor has been studied for decades, its role in membrane trafficking has been ambiguous. Here, we systematically investigated the localization and function of mammalian AP-1. This adaptor associates with the trans-Golgi network (TGN) and with TGN-related recycling endosomes. Disruption of the 1A subunit of AP-1 has only a mild effect on the Golgi export of secretory cargoes, but it causes depletion from the Golgi of multiple transmembrane TGN proteins. Live-cell imaging and a cell surface labeling assay indicate that when TGN proteins are unable to bind AP-1, they exit the Golgi to the plasma membrane. Our interpretation is that the vesicles generated with AP-1 recycle transmembrane TGN proteins, thereby keeping those proteins in the Golgi during cisternal maturation. The clathrin adaptor epsinR seems to function as a partner for AP-1 in recycling a subset of TGN proteins. These results closely align with studies of AP-1 function in yeast, suggesting that the conserved core role of AP-1 is the intra-Golgi recycling of TGN proteins.

cell biology↗

COPI-dependent intra-Golgi recycling at an intermediate stageof cisternal maturation

The traffic pathways that recycle resident Golgi proteins during cisternal maturation are not completely defined. We addressed this challenge using the yeast Saccharomyces cerevisiae, in which maturation of individual cisternae can be visualized directly. A new assay captures a specific population of Golgi-derived vesicles at the bud neck, thereby revealing which resident Golgi proteins are carried as cargo in those vesicles. This method supplies evidence for at least three classes of intra-Golgi vesicles with different cargo compositions. Consistent with our previously published data, one class of vesicles mediates a late pathway of intra-Golgi recycling with the aid of the AP-1 and Ent5 clathrin adaptors, and a second class of vesicles mediates an early pathway of intra-Golgi recycling with the aid of the COPI vesicle coat. Here, we identify another COPI-dependent pathway of intra-Golgi recycling and show that it operates kinetically between the two previously known pathways. Thus, intra-Golgi recycling is mediated by multiple COPI-dependent pathways followed by a clathrin-dependent pathway.

cell biology↗

Clathrin adaptors mediate two sequential pathwaysof intra-Golgi recycling

The pathways of membrane traffic within the Golgi apparatus are not fully known. This question was addressed using the yeast Saccharomyces cerevisiae, in which the maturation of individual Golgi cisternae can be visualized. We recently proposed that the AP-1 clathrin adaptor mediates intra-Golgi recycling late in the process of cisternal maturation. Here, we demonstrate that AP-1 cooperates with the Ent5 clathrin adaptor to recycle a set of Golgi transmembrane proteins. This recycling can be detected by removing AP-1 and Ent5, thereby diverting the AP-1/Ent5-dependent Golgi proteins into an alternative recycling loop that involves traffic to the plasma membrane followed by endocytosis. Unexpectedly, various AP-1/Ent5-dependent Golgi proteins show either intermediate or late kinetics of residence in maturing cisternae. We infer that the AP-1/Ent5 pair mediates two sequential intra-Golgi recycling pathways that define two classes of Golgi proteins. This insight can explain the polarized distribution of transmembrane proteins in the Golgi.

cell biology↗