Cooperation of GGAs and AP-1 in packaging MPRs at the trans-Golgi network.
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.
Doray
Balraj
B
Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Ghosh
Pradipta
P
Griffith
Janice
J
Geuze
Hans J
HJ
Kornfeld
Stuart
S
D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007739:L Cells; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; C407306:GGA adaptor proteins; D008565:Membrane Proteins; D017527:Receptor, IGF Type 2; D011994:Recombinant Proteins; D020727:ADP-Ribosylation Factors