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The early vertebrate Danio rerio Mr 46000 mannose-6-phosphate receptor: biochemical and functional characterisation

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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.

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Acknowledgements

The authors thank VWS, Hannover, Germany, for the support through a research grant to Prof. Dr. Siva Kumar, India, Prof. Dr. R. Pohlmann and Prof. Dr. von Figura, Germany, I/76098 and I/78913, and the Department of Biochemistry, University of Hyderabad, India, for support. We would like to thank Prof. Byrappa Venkatesh, Singapore, for his comments on the fish genome, Daniela Brinkmann for excellent technical assistance and Roberto Bresciani, University of Brescia, Italy, for providing the GFP human MPR 46 expression plasmid.

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Authors and Affiliations

  1. Protein Biochemistry Laboratory, Department of Biochemistry, University of Hyderabad, Hyderabad, 500 046, India

    Suresh Koduru, Suryanarayana Raju Vegiraju & Siva Kumar Nadimpalli

  2. Institut fuer Biochemie und Molekulare Zellbiologie, Heinrich Dueker Weg 12, 37073, Göttingen, Germany

    Kurt von Figura

  3. Institut fuer Physiologische Chemie und Pathobiochemie, University Hospital of Münster, Waldeyerstrasse 15, 48149, Münster, Germany

    Regina Pohlmann & André Dennes

Authors
  1. Suresh Koduru
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  2. Suryanarayana Raju Vegiraju
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  3. Siva Kumar Nadimpalli
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  4. Kurt von Figura
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  5. Regina Pohlmann
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  6. André Dennes
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Corresponding author

Correspondence to Regina Pohlmann.

Additional information

Communicated by M. Hammerschmidt

The zebrafish MPR 46 sequence data have been submitted to the GenBank database under accession no. DQ089037.

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Fig. S1

Analysis of generated MPR-deficient FLP-In cells. MPR-deficient MEF [mpr(-/-)]were stably transfected with pFRT/laczeo to generate a single FLPrecombinase target site (FRT). After selection with Zeocin stable foci (FLP2, FLP5, and FLP7) were screened by Southern blotting to identify those that have a single integration site. A 1100 bp EcoRI fragment from pFRT/laczeo was used as probe. Commercially available FLP-In-NIH3T3 cells were used as control (Invitrogen, Karlsruhe, Germany). (GIF 263 kb)

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Koduru, S., Vegiraju, S.R., Nadimpalli, S.K. et al. The early vertebrate Danio rerio Mr 46000 mannose-6-phosphate receptor: biochemical and functional characterisation. Dev Genes Evol 216, 133–143 (2006). https://doi.org/10.1007/s00427-005-0043-6

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  • DOI: https://doi.org/10.1007/s00427-005-0043-6

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