title: The early vertebrate Danio rerio Mr 46000 mannose-6-phosphate receptor: biochemical and functional characterisation.
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, gamma-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.
authors.affiliation: Protein Biochemistry Laboratory, Department of Biochemistry, University of Hyderabad, Hyderabad 500 046, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Koduru
authors.forename: Suryanarayana Raju
authors.initials: SR
authors.lastname: Vegiraju
authors.forename: Siva Kumar
authors.initials: SK
authors.lastname: Nadimpalli
authors.forename: Kurt
authors.initials: K
authors.lastname: von Figura
authors.forename: Regina
authors.initials: R
authors.lastname: Pohlmann
authors.forename: André
authors.initials: A
authors.lastname: Dennes
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002402:Cathepsin D / Q000378:metabolism; D002417:Cattle; D002645:Chickens / Q000235:genetics; D003001:Cloning, Molecular; D005399:Fishes / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000235:genetics* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014981:Xenopus / Q000235:genetics; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C407306:GGA adaptor proteins; D011506:Proteins; D017527:Receptor, IGF Type 2; D029961:Zebrafish Proteins; C018589:lysosomal proteins; D002402:Cathepsin D; D020727:ADP-Ribosylation Factors