title: Basolateral sorting of LDL receptor in MDCK cells: the cytoplasmic domain contains two tyrosine-dependent targeting determinants.
abstract: In MDCK cells, transport of membrane proteins to the basolateral plasma membrane has been shown to require a distinct cytoplasmic domain determinant. Although the determinant is often related to signals used for localization in clathrin-coated pits, inactivation of the coated pit domain in the human LDL receptor did not affect basolateral targeting. By expressing mutant and chimeric LDL receptors, we have now identified two independently acting signals that are individually sufficient for basolateral targeting. The two determinants mediate basolateral sorting with different efficiencies, but both contain tyrosine residues critical for activity. The first determinant was colinear with, but distinct from, the coated pit domain of the receptor. The second was found in the C-terminal region of the cytoplasmic domain of the receptor and, although tyrosine-dependent, did not mediate endocytosis. The results suggest that membrane proteins can have functionally redundant signals for basolateral transport and that a tyrosine-containing motif may be a common feature of multiple intracellular sorting events.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: K
authors.initials: K
authors.lastname: Matter
authors.forename: W
authors.initials: W
authors.lastname: Hunziker
authors.forename: I
authors.initials: I
authors.lastname: Mellman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism; D004285:Dogs; D004705:Endocytosis; D008969:Molecular Sequence Data; D017452:Receptors, IgG / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000502:physiology
chemical_list: D017452:Receptors, IgG; D011973:Receptors, LDL; D011993:Recombinant Fusion Proteins; D014443:Tyrosine