Tail-specific antibodies that block return of 46,000 M(r) mannose 6-phosphate receptor to the trans-Golgi network

Schulze-Garg, Christine; Böker, Christian; Nadimpalli, Siva Kumar; Figura, Kurt Von; Hille-Rehfeld, Annette

doi:10.1083/jcb.122.3.541

Cited by 27 publications

(10 citation statements)

References 39 publications

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“…It has been shown that microinjection of a short MPR46 tail peptide comprising the dileucine signal leads to missorting of MPR46 into an endosomal compartment and to a block in the return of the receptor to the TGN (31). Consistent with this observation the ultrastructural and biochemical data presented here show the importance of the dileucine motif for endosomal sorting of MPR46.…”

Section: The Dileucine Motif As a Determinant For Endosomal Sorting Osupporting

confidence: 87%

The Dileucine Motif Within the Tail of MPR46 is Required for Sorting of the Receptor in Endosomes

Tikkanen

Obermüller

Denzer

et al. 2000

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The cytoplasmic tail of MPR46 carries a leucine-based motif that is required for the sorting of lysosomal enzymes by the receptor. In addition, it is one of three independent, but functionally redundant, internalization signals present in the cytoplasmic tail of MPR46. We have analyzed a mutant of MPR46, in which the dileucine pair was replaced by alanines (MPR46 LL/AA) with respect to its intracellular distribution and trafficking. Ultrastructural analysis of cells expressing the MPR46 LL/AA mutant revealed that the substitution of the dileucine pair causes a shift of the receptor distribution from the TGN, where it is packaged into AP1-containing vesicles, to vesicular structures distributed throughout the cytoplasm. The vesicles could be identified as early endosomes with internalized BSA-gold and rab5 as markers. By analyzing the receptor trafficking biochemically, we found that return of the LL/AA mutant receptor from the plasma membrane/endosome pool back to the TGN was impaired, while recycling from endosomes to the plasma membrane was enhanced. In conclusion, our data indicate that the dileucine motif in the MPR46 tail is required for a sorting event in endosomes.

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Section: The Dileucine Motif As a Determinant For Endosomal Sorting Osupporting

confidence: 87%

The Dileucine Motif Within the Tail of MPR46 is Required for Sorting of the Receptor in Endosomes

Tikkanen

Obermüller

Denzer

et al. 2000

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“…Our results, therefore, indicate that although the exit of CI-MPR from the endocytic pathway toward the TGN seems to be perturbed by dynK44A overexpression, the CI-MPR is not missorted to lysosomes but accumulates in a prelysosomal compartment. Similarly, Schulze-Garg et al (1993) reported that, after injection of specific antibodies against its cytoplasmic tail, the CD-MPR (the 46-kDa MPR) redistributed to an intermediate compartment on the endocytic pathway in which the receptor segregated from materials destined to lysosomes.…”

Section: Discussionmentioning

confidence: 99%

Role for Dynamin in Late Endosome Dynamics and Trafficking of the Cation-independent Mannose 6-Phosphate Receptor

Nicoziani

Vilhardt

Llorente

et al. 2000

MBoC

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It is well established that dynamin is involved in clathrin-dependent endocytosis, but relatively little is known about possible intracellular functions of this GTPase. Using confocal imaging, we found that endogenous dynamin was associated with the plasma membrane, the trans-Golgi network, and a perinuclear cluster of cation-independent mannose 6-phosphate receptor (CI-MPR)-containing structures. By electron microscopy (EM), it was shown that these structures were late endosomes and that the endogenous dynamin was preferentially localized to tubulovesicular appendices on these late endosomes. Upon induction of the dominant-negative dynK44A mutant, confocal microscopy demonstrated a redistribution of the CI-MPR in mutantexpressing cells. Quantitative EM analysis of the ratio of CI-MPR to lysosome-associated membrane protein-1 in endosome profiles revealed a higher colocalization of the two markers in dynK44A-expressing cells than in control cells. Western blot analysis showed that dynK44A-expressing cells had an increased cellular procathepsin D content. Finally, EM revealed that in dynK44A-expressing cells, endosomal tubules containing CI-MPR were formed. These results are in contrast to recent reports that dynamin-2 is exclusively associated with endocytic structures at the plasma membrane. They suggest instead that endogenous dynamin also plays an important role in the molecular machinery behind the recycling of the CI-MPR from endosomes to the trans-Golgi network, and we propose that dynamin is required for the final scission of vesicles budding from endosome tubules. INTRODUCTIONThe cation-independent mannose 6-phosphate receptor (CI-MPR) transports newly synthesized lysosomal enzymes from the trans-Golgi network (TGN) to endosomes, where the acidic pH causes release of the ligand, making the receptor free to recycle to the TGN (Duncan and Kornfeld, 1988;Goda and Pfeffer, 1988). The CI-MPR recycling from endosomes to the TGN seems to be a strictly controlled event. Rab9 is essential for the transport between endosomes and the TGN (Lombardi et al., 1993;Riederer et al., 1994;Diaz et al., 1997), and ␣-SNAP and NSF stimulate the in vitro transport of CI-MPR from endosomes (Itin et al., 1997). Although budding of clathrin-coated vesicles from endosomes has been reported (Stoorvogel et al., 1996), clathrin does not seem to be required for the transport of CI-MPR from late endosomes to the TGN (Draper et al., 1990;Goda and Pfeffer, 1991) in a reconstituted cell-free system (Goda and Pfeffer, 1988). Recently, a new protein, called TIP47, was found to be important for the endosomal sorting of CI-MPR, probably by acting in cargo selection (Diaz and Pfeffer, 1998). The recruitment of TIP47 is enhanced in the presence of GTP␥S, indicating that a GTPase could be involved in the budding step (Diaz and Pfeffer, 1998). The budding step also seems to require ETF-1, an N-ethylmaleimide-sensitive factor different from NSF (Goda and Pfeffer, 1991). ETF-1 is needed at an early stage of the formation of recycling vesicles, and ...

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“…Some support for this notion has come from the study of Green et al (1994) that demonstrated that P-selectin contains a signal in its cytoplasmic tail that is necessary for efficient delivery to lysosomes. In contrast, experiments with microinjected antibodies specific for the cytoplasmic tail of the CD-MPR have led to the suggestion that recycling from endosomes to the Golgi complex is signal mediated (Schulze-Garg et al, 1993). Consistent with this view, an immunoelectron microscopy study of HepG2 and BHK cells revealed that the CD-MPR and the asialoglycoprotein receptor are sequestered into separate tubular-vesicular structures associated with endosomes (Klumpermann et al, 1993).…”

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confidence: 99%

A determinant in the cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor prevents trafficking to lysosomes.

Rohrer

Schweizer

Johnson

et al. 1995

The Journal of Cell Biology

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Abstract. The bovine cation-dependent mannose 6-phosphate receptor (CD-MPR) is a type 1 transmembrane protein that cycles between the trans-Golgi network, endosomes, and the plasma membrane. When the terminal 40 residues were deleted from the 67-amino acid cytoplasmic tail of the CD-MPR, the half-life of the receptor was drastically decreased and the mutant receptor was recovered in lysosomes. Analysis of additional cytoplasmic tail truncation mutants and alanine-scanning mutants implicated amino acids 34-39 as being critical for avoidance of lysosomal degradation. The cytoplasmic tail of the CD-MPR was partially effective in preventing the lysosomal membrane protein Lampl from entering lysosomes. Complete exclusion required both the CD-MPR cytoplasmic tail and transmembrane domain. The transmembrane domain alone had just a minor effect on the distribution of Lamp1. These findings indicate that the cytoplasmic tail of the CD-MPR contains a signal that prevents the receptor from trafficking to lysosomes. The transmembrane domain of the CD-MPR also contributes to this function.

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Tail-specific antibodies that block return of 46,000 M(r) mannose 6-phosphate receptor to the trans-Golgi network

Cited by 27 publications

References 39 publications

The Dileucine Motif Within the Tail of MPR46 is Required for Sorting of the Receptor in Endosomes

The Dileucine Motif Within the Tail of MPR46 is Required for Sorting of the Receptor in Endosomes

Role for Dynamin in Late Endosome Dynamics and Trafficking of the Cation-independent Mannose 6-Phosphate Receptor

A determinant in the cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor prevents trafficking to lysosomes.

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