The MHC Class II-Associated Chicken Invariant Chain Shares Functional Properties with Its Mammalian Homologs

Bremnes, Bjørn; Rode, Marit; Gedde-Dahl, Merete; Nordeng, Tommy W.; Jacobsen, Johanne T.; Ness, Scott A.; Bakke, Oddmund

doi:10.1006/excr.2000.4985

Cited by 30 publications

(27 citation statements)

References 61 publications

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“…The LL/LI signal is present in various molecules, such as the tyrosine kinase receptors (Hanks et al, 1988), in addition to the T-cell receptor (Letourneur and Klausner, 1992) and the two M6PR (Johnson and Kornfeld, 1992). These results are in agreement with a previous observation about leucine-based targeting motifs in mammals and poultry (Bremnes et al, 1994(Bremnes et al, , 2000Xu et al, 2008). Nilsson et al (1991) suggested that the cytoplasmic Ii tail is exchanged with that of galactosyltransferase, which contains a di-leucine, and the resulting molecule is sorted to endosomes.…”

Section: Two Leucine-based Motifs Are Endosomal Targeting Signalsupporting

confidence: 93%

Molecular cloning and site-directed mutagenesis of leucine-based sorting motifs of the porcine invariant chain

Dai²,

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Invariant chain (Ii) is a transmembrane protein that associates with MHC class II molecules in the endoplasmic reticulum. The cytoplasmic tail of Ii contains two leucine residues able to direct Ii to the endocytic pathway. We obtained the pig Ii gene by RT-PCR. Mutated Ii was prepared via site directed mutagenesis by the PCR Megaprimer method to study the effect of the two leucines on the localization of pig Ii. These mutated fragments were ligated to the vector pmCherry-C1. The recombinant plasmids were transiently transfected into COS-7 cells with Lipofectamine TM 2000. Fluorescence of fusion proteins (mCherry-Ii) was observed with a fluorescent microscope. Amino acid sequence alignment showed that pig Ii has domains similar to those seen in other mammalian Ii, including the cytoplasmic, transmembrane, class II-associated Ii-derived peptide, and trimerization domains. Based on observations with the fluorescent microscope, we found that two leucine-based motifs are required for pig Ii intracellular localization, and that both motifs independently mediate this function in Ii.

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Section: Two Leucine-based Motifs Are Endosomal Targeting Signalsupporting

confidence: 93%

Molecular cloning and site-directed mutagenesis of leucine-based sorting motifs of the porcine invariant chain

Dai²,

et al. 2013

Genet. Mol. Res.

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“…By contrast, inactivation of the LTSs of other transmembrane proteins and receptors caused no more than a 3-fold reduction of targeting compared with that of the intact protein, suggesting that additional sequences may be involved in those cases (9,27,29,43). The existence of multiple lysosomal sorting signals has indeed been demonstrated for ␥ and ␦ chains of CD3 (48), for the invariant chain (Ii) of class II major histocompatibility complex (49) and EGFR (27)(28)(29). In principal, by acting in concert, multiple LTSs could provide for a targeting activity equivalent to that of KCPL within P-selectin.…”

Section: Discussionmentioning

confidence: 99%

Lysosomal Targeting of P-selectin Is Mediated by a Novel Sequence within Its Cytoplasmic Tail

Blagoveshchenskaya

Norcott

Cutler

1998

Journal of Biological Chemistry

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Signals controlling the intracellular targeting of many membrane proteins are present as short sequences within their cytoplasmic domains. P-selectin is a type I membrane protein receptor for leukocytes, acting during the inflammation response. Heterologous expression experiments have demonstrated that its 35-residue cytoplasmic tail contains signals for targeting to synaptic-like microvesicles, dense-cored granules, and lysosomes. We have examined the lysosomal targeting information present within the cytoplasmic tail by sitedirected mutagenesis of horseradish peroxidase-P-selectin chimeras followed by transient transfection in H.Ep.2 cells. Assaying lysosomal targeting by subcellular fractionation as well as intracellular proteolysis, we have discovered a novel lysosomal targeting signal, KCPL, located within the C1 domain of the cytoplasmic tail. Alanine substitution of this tetrapeptide reduced lysosomal targeting to the level of a tailless horseradish peroxidase-P-selectin chimera, which was previously found to be deficient in both internalization and delivery to lysosomes. A proline residue within this lysosomal targeting signal makes a major contribution to the efficiency of lysosomal targeting. A diaminobenzidine density shift procedure established that chimeras with an inactivated KCPL sequence are present within transferrin-positive compartments. Such a mutant also displays an increased level of expression at the plasma membrane. Our results indicate that the sequence KCPL within the cytoplasmic tail of P-selectin is a structural element that mediates sorting from endosomes to lysosomes.

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“…The tyrosine-based signals are generally in the form of YXX⌽, where X and ⌽ are bulky and hydrophobic amino acids, respectively. Dileucine motifs are more flexible, because a substitution of one leucine by isoleucine, methionine, or valine does not result in a loss of signal efficiency (7)(8)(9). Sorting is thought to occur by interaction of these signals with clathrin-coated vesicle adapter proteins (for a review see Ref.…”

mentioning

confidence: 99%

Targeting of NPC1 to Late Endosomes Involves Multiple Signals, Including One Residing within the Putative Sterol-sensing Domain

Scott

Higgins

Davies

et al. 2004

Journal of Biological Chemistry

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The NPC1 protein is a multipass transmembrane protein whose deficiency causes the autosomal recessive lipid storage disorder Niemann-Pick type C1. NPC1 localizes predominantly to late endosomes and has a dileucine motif located within a small cytoplasmic tail thought to target the protein to this location. Our data have suggested previously that the protein can reach its correct location in the absence of its cytoplasmic tail, suggesting that other signals contribute to NPC1 targeting. By using various FLAG-tagged and CD32-NPC1 chimeric fusion constructs, we show that multiple signals are responsible for the trafficking of NPC1 to the endosomal compartment, including the dileucine motif and a previously unidentified signal residing within the putative sterol-sensing domain transmembrane domain 3. Neither region alone was capable of directing heterologous CD32 fusions to late endosomes exclusively via the trans-Golgi network to the late endosome route taken by wild-type NPC1; transmembrane domain 3 was unable to maintain CD32 in late endosomes, indicating that two or more signals work in concert to target and retain NPC1 in this compartment. In addition we confirm that the tail dileucine motif is not essential for NPC1 targeting to late endosomes, and we discuss the implications of this finding along with the previously unappreciated role for transmembrane domain 3 in NPC1 localization and function.

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The MHC Class II-Associated Chicken Invariant Chain Shares Functional Properties with Its Mammalian Homologs

Cited by 30 publications

References 61 publications

Molecular cloning and site-directed mutagenesis of leucine-based sorting motifs of the porcine invariant chain

Molecular cloning and site-directed mutagenesis of leucine-based sorting motifs of the porcine invariant chain

Lysosomal Targeting of P-selectin Is Mediated by a Novel Sequence within Its Cytoplasmic Tail

Targeting of NPC1 to Late Endosomes Involves Multiple Signals, Including One Residing within the Putative Sterol-sensing Domain

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