A single amino acid change in the cytoplasmic domain allows the influenza virus hemagglutinin to be endocytosed through coated pits

Lazarovits, Janette; Roth, Michael G.

doi:10.1016/0092-8674(88)90092-x

Cited by 237 publications

(208 citation statements)

References 27 publications

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“…Second site mutants of HAϩ8 were made by oligonucleotide directed mutagenesis on the same HAϩ8 template, and are named after the position and amino acid substitution made. Construction of the HA-Y543 mutant and second-site mutants of that protein has been previously reported (18,31). Wild type HA is referred to as HA wt.…”

Section: Methodsmentioning

confidence: 99%

“…1a). HA-Y543 has an internalization signal and undergoes internalization and recycling, with 60 -80% of the protein at the cell surface and 20 -40% internal at steady-state (18,19,31). As expected, HA-Y543 was present both at the cell surface and in intracellular vesicles distributed throughout the cytoplasm, and this pattern of location did not change during the 6-h treatment with cycloheximide, although the amount of HA-Y543 detected was observed to decrease (Fig.…”

Section: Haϩ8 Containing 8 Additional Amino Acids At the Carboxylmentioning

confidence: 99%

“…To compare the rate of internalization of HAϩ8 to that of the internalization-competent mutant HA-Y543 and the internalization-incompetent HA wt, CV-1 cells expressing each of these proteins were pulse-labeled 36 h after infection with recombinant virus vectors and the radioactive proteins were chased to the cell surface. Internalization of HAs was measured by an assay described previously that measures the amount of HA labeled with antibody at the cell surface that can be chased at 37°C to a location inaccessible to trypsin added at 4°C (17)(18)(19)32). The experiment was internally controlled by a sample of each protein that was never chased at 37°C.…”

Section: Haϩ8 Containing 8 Additional Amino Acids At the Carboxylmentioning

confidence: 99%

“…We have identified a series of mutant HAs that are internalized at very different rates. One, HA-Y543, has a single amino acid change in the cytoplasmic domain 4 amino acids from the carboxyl terminus, a substitution of tyrosine for cysteine at position 543 (18). When expressed in amounts that do not saturate the internalization capacity of CV-1 (19) or Madin-Darby canine kidney cells (20), this protein is internalized as rapidly as some well characterized cell surface receptors (21)(22)(23)(24) and interacts dynamically with coated pits (17).…”

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confidence: 99%

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Degradation of Mutant Influenza Virus Hemagglutinins Is Influenced by Cytoplasmic Sequences Independent of Internalization Signals

Zwart

Brewer

Lazarovits

et al. 1996

Journal of Biological Chemistry

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A mutant influenza virus hemagglutinin, HA؉8, having a carboxyl-terminal extension of 8 amino acids that included 4 aromatic residues, was internalized within 2 min of arriving at the cell surface and was degraded quickly by a process that was inhibited by ammonium chloride. Through second-site mutagenesis, the internalization sequence of HA؉8 was found to closely resemble the internalization signals of the transferrin receptor or large mannose 6-phosphate receptor. Comparison of the intracellular traffic of HA؉8 and a series of other HA mutants that differed in their rates of internalization revealed a relation between the amount of the protein on the plasma membrane at steady state and the internalization rate that would be predicted if most of each protein recycled to the cell surface. However, there was no simple correlation between the internalization rate and the rate of degradation, indicating that transport to the compartment where degradation occurred was not simply a function of the concentration of the proteins in early endosomes. The internal populations of both HA؉8, which was degraded with a t 1/2 of 1.9 h, and HA-Y543, which was degraded with a t 1/2 of 2.9 h, were found by cell fractionation and density-shift experiments to reside in early endosomes with little accumulation in lysosomes. A fluid-phase marker reached lysosomes 3-4-fold faster than these proteins were degraded. Degradation of these mutant HAs involved a rate-determining step in early endosomes that was sensitive to some feature of the protein that depended upon sequence differences in the cytoplasmic domain unrelated to the internalization signal.

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Section: Methodsmentioning

confidence: 99%

Section: Haϩ8 Containing 8 Additional Amino Acids At the Carboxylmentioning

confidence: 99%

Section: Haϩ8 Containing 8 Additional Amino Acids At the Carboxylmentioning

confidence: 99%

mentioning

confidence: 99%

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Degradation of Mutant Influenza Virus Hemagglutinins Is Influenced by Cytoplasmic Sequences Independent of Internalization Signals

Zwart

Brewer

Lazarovits

et al. 1996

Journal of Biological Chemistry

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“…Most tyrosine-based signals conform to the consensus motifs YXXΦ (Y is tyrosine, X is any amino acid and Φ is an amino acid with a bulky hydrophobic side chain) [67] or NPXY (N is asparagine and P is proline) [68][69][70][71]. It was shown by several groups that the substitution of tyrosine residues in the cytosolic domains of various endocytic receptors devoid of NPXY motifs impaired internalization [72][73][74][75][76][77]. NPXY signals have been shown to mediate only the rapid internalization of a subset of type I integral membrane proteins, and not mediate other intracellular sorting events.…”

Section: Endocytic and Sorting Signalsmentioning

confidence: 99%

Mutual Regulation of Receptor-Mediated Cell Signalling and Endocytosis: EGF Receptor System as an Example

Wang¹

2012

Molecular Regulation of Endocytosis

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Recognition of sorting signals by clathrin adaptors

1999

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Sorting of membrane proteins is generally mediated by cytosolic coats, which create a scaffold to form coated buds and vesicles and to selectively concentrate cargo by interacting with cytosolic signals. The classical paradigm is the interaction between clathrin coats and associated adaptor proteins, which cluster receptors with characteristic tyrosine and dileucine motifs during endocytosis. Clathrin in association with different sets of adaptors is found in addition at the trans‐Golgi network and endosomes. Sequences similar to internalization signals also direct lysosomal and basolateral sorting, which implicates related clathrin‐adaptor coats in the respective sorting pathways. This review concentrates on the recognition of sorting signals by clathrin‐associated adaptor proteins, an area of significant recent progress due to new methodological and conceptual approaches. BioEssays 21:558–567, 1999. © 1999 John Wiley & Sons, Inc.

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A single amino acid change in the cytoplasmic domain allows the influenza virus hemagglutinin to be endocytosed through coated pits

Cited by 237 publications

References 27 publications

Degradation of Mutant Influenza Virus Hemagglutinins Is Influenced by Cytoplasmic Sequences Independent of Internalization Signals

Degradation of Mutant Influenza Virus Hemagglutinins Is Influenced by Cytoplasmic Sequences Independent of Internalization Signals

Mutual Regulation of Receptor-Mediated Cell Signalling and Endocytosis: EGF Receptor System as an Example

Recognition of sorting signals by clathrin adaptors

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