The early vertebrate Danio rerio Mr 46000 mannose-6-phosphate receptor: biochemical and functional characterisation |
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Authors: | Suresh Koduru Suryanarayana Raju Vegiraju Siva Kumar Nadimpalli Kurt von Figura Regina Pohlmann André Dennes |
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Institution: | Protein Biochemistry Laboratory, Department of Biochemistry, University of Hyderabad, Hyderabad 500 046, India. |
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Abstract: | Mannose-6-phosphate receptors (MPRs) have been identified in a wide range of species from humans to invertebrates such as
molluscs. A characteristic of all MPRs is their common property to recognize mannose-6-phosphate residues that are labelling
lysosomal enzymes and to mediate their targeting to lysosomes in mammalian cells by the corresponding receptor proteins. We
present here the analysis of full-length sequences for MPR 46 from zebrafish (Danio rerio) and its functional analysis. This is the first non-mammalian MPR 46 to be characterised. The amino acid sequences of the
zebrafish MPR 46 displays 70% similarity to the human MPR 46 protein. In particular, all essential cysteine residues, the
transmembrane domain as well as the cytoplasmic tail residues harbouring the signals for endocytosis and Golgi-localizing,
γ-ear-containing, ARF-binding protein (GGA)-mediated sorting at the trans-Golgi network, are highly conserved. The zebrafish
MPR 46 has the arginine residue known to be essential for mannose-6-phosphate binding and other additional characteristic
residues of the mannose-6-phosphate ligand-binding pocket. Like the mammalian MPR 46, zebrafish MPR 46 binds to the multimeric
mannose-6-phosphate ligand phosphomannan and can rescue the missorting of lysosomal enzymes in mammalian MPR-deficient cells.
The conserved C-terminal acidic dileucine motif (DxxLL) in the cytoplasmic domain of zebrafish MPR 46 essential for the interaction
of the GGAs with the receptor domains interacts with the human GGA1-VHS domain. Interestingly, the serine residue suggested
to regulate the interaction between the tail and the GGAs in a phosphorylation-dependent manner is substituted by a proline
residue in fish.
Electronic Supplementary Material Supplementary material is available for this article at .
The zebrafish MPR 46 sequence data have been submitted to the GenBank database under accession no. DQ089037. |
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Keywords: | MPR 46 Fish Sorting GGAs |
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