Recognition of the tryptophan-based endocytosis signal in the neonatal Fc Receptor by the mu subunit of adaptor protein-2.
Endocytosis of membrane proteins is typically mediated by signals present in their cytoplasmic domains. These signals usually contain an essential tyrosine or pair of leucine residues. Both tyrosine- and dileucine-based endocytosis signals are recognized by the adaptor complex AP-2. The best understood of these interactions occurs between the tyrosine-based motif, YXXPhi, and the mu2 subunit of AP-2. We recently reported a tryptophan-based endocytosis signal, WLSL, contained within the cytoplasmic domain of the neonatal Fc receptor. This signal resembles YXXPhi. We have investigated the mechanism by which the tryptophan-based signal is recognized. Both interaction assays in vitro and endocytosis assays in vivo show that mu2 binds the tryptophan-based signal. Furthermore, the WLSL sequence binds the same site as YXXPhi. Unlike the WXXF motif, contained in stonin 2 and other endocytic proteins, WLSL does not bind the alpha subunit of AP-2. These observations reveal a functional similarity between the tryptophan-based endocytosis signal and the YXXPhi motif, and an unexpected versatility of mu2 function.
Wernick
Naomi L B
NL
Rosenstiel Center for Basic Biomedical Sciences and Department of Biology, Brandeis University, Waltham, Massachusetts 02254-9110, USA.
Haucke
Volker
V
Simister
Neil E
NE
D033962:Adaptor Protein Complex 2 / Q000378:metabolism* / Q000502:physiology; D033983:Adaptor Protein Complex mu Subunits / Q000378:metabolism* / Q000502:physiology; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004705:Endocytosis; D015395:Histocompatibility Antigens Class I; D011485:Protein Binding; D051381:Rats; D011961:Receptors, Fc / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014364:Tryptophan
D033962:Adaptor Protein Complex 2; D033983:Adaptor Protein Complex mu Subunits; D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; C438886:adaptor protein complex 2, mu 2 subunit; D014364:Tryptophan; C100688:Fc receptor, neonatal