P4-ATPase requirement for AP-1/clathrin function in protein transport from the trans-Golgi network and early endosomes.

Liu K, Surendhran K, Nothwehr SF, Graham TR
Mol Biol Cell. 2008 19 (8): 3526-35

PMID: 18508916 · PMCID: PMC2488278 · DOI:10.1091/mbc.e08-01-0025

Drs2p is a resident type 4 P-type ATPase (P4-ATPase) and potential phospholipid translocase of the trans-Golgi network (TGN) where it has been implicated in clathrin function. However, precise protein transport pathways requiring Drs2p and how it contributes to clathrin-coated vesicle budding remain unclear. Here we show a functional codependence between Drs2p and the AP-1 clathrin adaptor in protein sorting at the TGN and early endosomes of Saccharomyces cerevisiae. Genetic criteria indicate that Drs2p and AP-1 operate in the same pathway and that AP-1 requires Drs2p for function. In addition, we show that loss of AP-1 markedly increases Drs2p trafficking to the plasma membrane, but does not perturb retrieval of Drs2p from the early endosome back to the TGN. Thus AP-1 is required at the TGN to sort Drs2p out of the exocytic pathway, presumably for delivery to the early endosome. Moreover, a conditional allele that inactivates Drs2p phospholipid translocase (flippase) activity disrupts its own transport in this AP-1 pathway. Drs2p physically interacts with AP-1; however, AP-1 and clathrin are both recruited normally to the TGN in drs2Delta cells. These results imply that Drs2p acts independently of coat recruitment to facilitate AP-1/clathrin-coated vesicle budding from the TGN.

MeSH Terms (16)

Alleles Biological Transport Calcium-Transporting ATPases Cell Membrane Clathrin Endosomes Exocytosis Gene Expression Regulation, Fungal Golgi Apparatus Green Fluorescent Proteins Lipid Bilayers Models, Biological Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins trans-Golgi Network Transcription Factor AP-1

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