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Science 6 September 2002:
Vol. 297. no. 5587, pp. 1700 - 1703
DOI: 10.1126/science.1075327

Reports

Cooperation of GGAs and AP-1 in Packaging MPRs at the Trans-Golgi Network

Balraj Doray,1*dagger Pradipta Ghosh,1* Janice Griffith,2 Hans J. Geuze,2 Stuart Kornfeld1ddagger

The Golgi-localized, gamma -ear-containing, adenosine diphosphate ribosylation factor-binding proteins (GGAs) are multidomain proteins that bind mannose 6-phosphate receptors (MPRs) in the Golgi and have an essential role in lysosomal enzyme sorting. Here the GGAs and the coat protein adaptor protein-1 (AP-1) were shown to colocalize in clathrin-coated buds of the trans-Golgi networks of mouse L cells and human HeLa cells. Binding studies revealed a direct interaction between the hinge domains of the GGAs and the gamma -ear domain of AP-1. Further, AP-1 contained bound casein kinase-2 that phosphorylated GGA1 and GGA3, thereby causing autoinhibition. This could induce the directed transfer of the MPRs from GGAs to AP-1. MPRs that are defective in binding to GGAs are poorly incorporated into AP-1-containing clathrin-coated vesicles. Thus, the GGAs and AP-1 interact to package MPRs into AP-1-containing coated vesicles.

1 Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
2 Department of Cell Biology, University Medical Center and Institute for Biomembranes, Utrecht University, 3584 CX Utrecht, Netherlands.
*   These authors contributed equally to this work.

dagger    Present address: Genome Institute of Singapore, 1 Science Park Road, The Capricorn #05-01 Singapore 117528.

ddagger    To whom correspondence should be addressed. E-mail: skornfel{at}im.wustl.edu


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