AP-1 membrane-cytoplasm recycling regulated by mu1A-adaptin.
The adaptor protein complex AP-1 mediates vesicular protein sorting between the trans Golgi network and endosomes. AP-1 recycles between membranes and the cytoplasm together with clathrin during transport vesicle formation and vesicle uncoating. AP-1 recycles independent of clathrin, indicating binding to unproductive membrane domains and premature termination of vesicle budding. Membrane recruitment requires ADP ribosylation factor-1-GTP, a transmembrane protein containing an AP-1-binding motif and phosphatidyl-inositol phosphate (PI-4-P). Little is known about the regulation of AP-1 membrane-cytoplasm recycling. We identified the N-terminal domain of micro1A-adaptin as being involved in the regulation of AP-1 membrane-cytoplasm recycling by constructing chimeras of micro1A and its homologue micro2. The AP-1* complex containing this mu2-micro1A chimera had slowed down recycling kinetics, resulting in missorting of mannose 6-phosphate receptors. The N-terminal domain is only accessible from the cytoplasmic AP-1 surface. None of the proteins known to influence AP-1 membrane recycling bound to this micro1A domain, indicating the regulation of AP-1 membrane-cytoplasm recycling by an yet unidentified cytoplasmic protein.
Medigeshi
Guruprasad R
GR
Center for Biochemistry and Moleculare Cell Biology, Georg-August-University Göttingen, Biochemie II, Heinrich-Düker-Weg 12, D-37073 Göttingen, Germany.
Krikunova
Maria
M
Radhakrishnan
Karthikeyan
K
Wenzel
Dirk
D
Klingauf
Jürgen
J
Schu
Peter
P
D033961:Adaptor Protein Complex 1 / Q000378:metabolism*; D033983:Adaptor Protein Complex mu Subunits / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism; D003001:Cloning, Molecular; D018699:Coated Vesicles / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D006056:Golgi Apparatus / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D008958:Models, Molecular; D021381:Protein Transport; D020798:Two-Hybrid System Techniques; D015003:Yeasts / Q000378:metabolism
D033961:Adaptor Protein Complex 1; D033983:Adaptor Protein Complex mu Subunits; C499063:Ap1m1 protein, mouse; D002966:Clathrin