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Science 6 September 2002: Vol. 297. no. 5587, pp. 1700 - 1703 DOI: 10.1126/science.1075327
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Reports
Cooperation of GGAs and AP-1 in Packaging MPRs at the Trans-Golgi Network
Balraj Doray,1*
Pradipta Ghosh,1*
Janice Griffith,2
Hans J. Geuze,2
Stuart Kornfeld1
The Golgi-localized, -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 -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.
Present address: Genome Institute of Singapore, 1 Science Park Road, The Capricorn #05-01 Singapore 117528.
To whom correspondence should be addressed. E-mail:
skornfel{at}im.wustl.edu
Read the Full Text
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