Tyrosine-based endocytic motifs stimulate oligomerization of AP-2 adaptor complexes.
The clathrin adaptor complex AP-2 functions in the assembly of clathrin-coated vesicles at the plasma membrane where it serves to couple endocytic vesicle formation to the selection of membrane cargo proteins. Recent evidence suggests that binding of tyrosine-based endocytic sorting motifs may induce a conformational change within the AP-2 adaptor complex that could enhance its interaction with other cargo molecules and with the membrane. We report here that soluble tyrosine-based endocytic sorting motif peptides facilitate clathrin/AP-2 recruitment to liposomal membranes and induce adaptor oligomerization even in the absence of a lipid bilayer. These effects are specific for endocytic motifs of the type Yxxphi whereas peptides corresponding to NPxY- or di-leucine-containing sorting signals are ineffective. Our data may help to explain how the highly cooperative assembly of clathrin and adaptors could be linked to the selection of membrane cargo proteins.
Haucke
Volker
V
Zentrum Biochemie and Molekulare Zellbiologie, Department of Biochemistry II, University of Göttingen, Göttingen, Germany. vhaucke@gwdg.de
Krauss
Michael
M
D033962:Adaptor Protein Complex 2 / Q000378:metabolism*; D033965:Adaptor Protein Complex alpha Subunits / Q000378:metabolism; D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000187:drug effects / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D005057:Eukaryotic Cells / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D011108:Polymers / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D022161:Transport Vesicles / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D033962:Adaptor Protein Complex 2; D033965:Adaptor Protein Complex alpha Subunits; D008081:Liposomes; D010455:Peptides; D011108:Polymers; D014443:Tyrosine