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Cited by 149

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A His-Leu-Leu sequence near the carboxyl terminus of the cytoplasmic domain of the cation-dependent mannose 6-phosphate receptor is necessary for the lysosomal enzyme sorting function.

Johnson, K.F., Kornfeld, S·1992·Journal of Biological Chemistry
DOI 10.1016/s0021-9258(18)41900-x
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Abstract

The determinants on the cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor (CD-MPR) required for lysosomal enzyme sorting have been analyzed. Mouse L cells deficient in the mannose 6-phosphate/insulin-like growth factor-II receptor were transfected with normal bovine CD-MPR cDNA or cDNAs containing mutations in the 67-amino acid cytoplasmic tail and assayed for their ability to target the lysosomal enzyme cathepsin D to lysosomes. Cells expressing the wild-type bovine CD-MPR sorted 67 +/- 2% of newly synthesized cathepsin D compared with the base-line value of 47 +/- 1%. The presence of mannose 6-phosphate in the medium did not affect the efficiency of cathepsin D sorting, indicating that the routing of the ligand-receptor complex is completely intracellular. Mutant receptors with the carboxyl-terminal His-Leu-Leu-Pro-Met67 residues deleted or replaced with alanines sorted cathepsin D below the base-line value. A mutant receptor with the outermost Pro-Met residues replaced with alanines sorted cathepsin D better than the wild-type receptor, indicating that the essential residues for sorting are the His-Leu-Leu sequence. Disruption of a putative casein kinase II phosphorylation site at Ser57 had no detectable effect on sorting. The mutant receptor with the five-amino acid deletion was able to bind to a phosphopentamannose affinity column, proving that its ligand binding site was grossly intact. Resialylation experiments showed that this mutant receptor recyc…

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  • The C-terminal segment of sortilin's cytoplasmic tail is closely related to the corresponding functionally important segment of MPR300.

    “the C-terminal segment in sortilin's cytoplasmic tail is closely related to the corresponding and functionally important segment of the cation-independent mannose 6-phosphate receptor (MPR300) (Johnson and Kornfeld, 1992a,b).”

    From The sortilin cytoplasmic tail conveys Golgi–endosome transport and binds the VHS domain of the GGA2 sorting protein (2001) · cites this paper as Johnson and Kornfeld, 1992a,b

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Research works printed but not linked: 34

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Metadata

Authors
Johnson, K. F., & Kornfeld, S.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1992-10
Volume
267
Issue
24
Pages
17110-17115
ISSN
0021-9258
DOI
10.1016/s0021-9258(18)41900-x
Cited by
149
References
1
Language
en
Licence

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