Abstract
The endosome/lysosome system plays key roles in embryonic development, but difficulties posed by inaccessible mammalian embryos have hampered detailed studies. The accessible, transparent embryos of Danio rerio, together with the genetic and experimental approaches possible with this organism, provide many advantages over rodents. In mammals, mannose 6-phosphate receptors (MPRs) target acid hydrolases to endosomes and lysosomes, but nothing is known of acid hydrolase targeting in zebrafish. Here, we describe the sequence of the zebrafish cation-dependent MPR (CD-MPR) and cation-independent MPR (CI-MPR), and compare them with their mammalian orthologs. We show that all residues critical for mannose 6-phosphate (M6P) recognition are present in the extracellular domains of the zebrafish receptors, and that trafficking signals in the cytoplasmic tails are also conserved. This suggests that the teleost receptors possess M6P binding sites with properties similar to those of mammalian MPRs, and that targeting of lysosomal enzymes by MPRs represents an ancient pathway in vertebrate cell biology. We also determined the expression patterns of the CD-MPR and CI-MPR during embryonic development in zebrafish. Both genes are expressed from the one-cell stage through to the hatching period. In early embryos, expression is ubiquitous, but in later stages, expression of both receptors is restricted to the anterior region of the embryo, covering the forebrain, midbrain and hindbrain. The expression patterns suggest time- and tissue-specific functions for the receptors, with particular evidence for roles in neural development. Our study establishes zebrafish as a novel, genetically tractable model for in vivo studies of MPR function and lysosome biogenesis.
Abbreviations
- M6P:
-
Mannose 6-phosphate
- MPR:
-
Mannose 6-phosphate receptor
- CD-MPR:
-
Cation-dependent MPR
- CI-MPR:
-
Cation-independent MPR
- HPF:
-
Hours post-fertilization
- IGF:
-
Insulin-like growth factor
- TGN:
-
trans-Golgi network
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Acknowledgements
We acknowledge the results of the Sanger Center ‘Human BLAST against Zebrafish’ search for the initial sequence data used in this study and the assistance of Catherine Glynn and Cathal MacConfhaola. This research was funded by Enterprise Ireland (IC/2003/20 to C.M.N. and SC/02/448 to L.B./C.M.N.), Millenium Fund, NUI Galway (E.E./L.B.), IRCSET Embark (K.McC) and the Health Research Board (RP/92/2002 to C.M.N./L.B.).
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Communicated by M. Hammerschmidt
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Nolan, C.M., McCarthy, K., Eivers, E. et al. Mannose 6-phosphate receptors in an ancient vertebrate, zebrafish. Dev Genes Evol 216, 144–151 (2006). https://doi.org/10.1007/s00427-005-0046-3
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DOI: https://doi.org/10.1007/s00427-005-0046-3