Tryptophan- and dileucine-based endocytosis signals in the neonatal Fc receptor.
The neonatal Fc receptor, FcRn, transports immunoglobulin G across intestinal cells in suckling rats. FcRn enters these cells by endocytosis and is present on the apical and basolateral surfaces. We investigated the roles of aromatic amino acids and a dileucine motif in the cytoplasmic domain of rat FcRn. We expressed mutant FcRn in which alanine replaced Trp-311, Leu-322, and Leu-323, or Phe-340 in the inner medullary collecting duct cell line IMCD. Individual replacement of the aromatic amino acids or the dileucine motif only partially blocked endocytosis of (125)I-Fc, whereas uptake by FcRn containing alanine residues in place of both Trp-311 and the dileucine motif was reduced to the level obtained with the tailless receptor. Leu-314 was required for the function of the tryptophan-based endocytosis signal, and Asp-317 and Asp-318 were required for the dileucine-based signal. Nonvectorial delivery of newly synthesized FcRn to the two cell surfaces was unaffected by loss of the endocytosis signals. However, the steady-state distribution of endocytosis mutants was predominantly apical, unlike wild-type FcRn, which was predominantly basolateral. This shift appeared to arise because the loss of endocytosis signals inhibited apical to basolateral transcytosis of FcRn more than basolateral to apical transcytosis.
Wu
Z
Z
Rosenstiel Center for Basic Biomedical Sciences, W. M. Keck Institute for Cellular Visualization, Brandeis University, Waltham, MA 02254-9110, USA.
Simister
N E
NE
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D004705:Endocytosis; D015395:Histocompatibility Antigens Class I; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D007700:Kinetics; D007930:Leucine / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation; D051381:Rats; D011961:Receptors, Fc / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014364:Tryptophan / Q000737:chemistry
D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; D014364:Tryptophan; D007930:Leucine; C100688:Fc receptor, neonatal