Arf regulates interaction of GGA with mannose-6-phosphate receptor.
The role of ADP-ribosylation factor (Arf) in Golgi associated, gamma-adaptin homologous, Arf-interacting protein (GGA)-mediated membrane traffic was examined. GGA is a clathrin adaptor protein that binds Arf through its GAT domain and the mannose-6-phosphate receptor through its VHS domain. The GAT and VHS domains interacted such that Arf and mannose-6-phosphate receptor binding to GGA were mutually exclusive. In vivo, GGA bound membranes through either Arf or mannose-6-phosphate receptor. However, mannose-6-phosphate receptor excluded Arf from GGA-containing structures outside of the Golgi. These data are inconsistent with predictions based on the model for Arf's role in COPI veside coat function. We propose that Arf recruits GGA to a membrane and then, different from the current model, 'hands-off' GGA to mannose-6-phosphate receptor. GGA and mannose-6-phosphate receptor are then incorporated into a transport intermediate that excludes Arf.
Hirsch
Dianne Snow
DS
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bldg 37 Room 6032 and Cell Biology and Metabolism Branch, National Institute of Child Health and Development, National Institutes of Health, Bethesda. MD 20892, USA.
Stanley
Katherine T
KT
Chen
Ling-Xin
LX
Jacques
Kerry M
KM
Puertollano
Rosa
R
Randazzo
Paul A
PA
D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D017527:Receptor, IGF Type 2 / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; C407306:GGA adaptor proteins; D017527:Receptor, IGF Type 2; D020727:ADP-Ribosylation Factors