Published online February 4, 2008
doi:10.1083/jcb.200709037
The Journal of Cell Biology, Vol. 180, No. 3, 467-472
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Lee et al.
Binding of cargo sorting signals to AP-1 enhances its association with ADP ribosylation factor 1–GTP
Intaek Lee,
Balraj Doray,
Jennifer Govero, and
Stuart Kornfeld
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110
Correspondence to Stuart Kornfeld: skornfel{at}im.wustl.edu
The adaptor protein AP-1 is the major coat protein involved in the formation of clathrin-coated vesicles at the trans-Golgi network. The prevailing view is that AP-1 recruitment involves coincident binding to multiple low-affinity sites comprising adenosine diphosphate ribosylation factor 1 (Arf-1)–guanosine triphosphate (GTP), cargo sorting signals, and phosphoinositides. We now show that binding of cargo signal peptides to AP-1 induces a conformational change in its core domain that greatly enhances its interaction with Arf-1–GTP. In addition, we provide evidence for cross talk between the dileucine and tyrosine binding sites within the AP-1 core domain such that binding of a cargo signal to one site facilitates binding to the other site. The stable association of AP-1 with Arf-1–GTP, which is induced by cargo signals, would serve to provide sufficient time for adaptor polymerization and clathrin recruitment while ensuring the packaging of cargo molecules into the forming transport vesicles.
I. Lee and B. Doray contributed equally to this paper.
Abbreviations used in this paper: Arf-1, ADP ribosylation factor 1; BAC, bovine adrenal cytosol; BBC, bovine brain cytosol; CCV, clathrin-coated vesicle; CI-MPR, cation-independent mannose 6-phosphate receptor; WT, wild-type.
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