Mannose 6-phosphate receptors in an ancient vertebrate, zebrafish |
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Authors: | Catherine M Nolan Karena McCarthy Edward Eivers Randy L Jirtle Lucy Byrnes |
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Institution: | (1) School of Biological and Environmental Science, University College Dublin, Belfield, Dublin, 4, Ireland;(2) Biochemistry Department, National University of Ireland, Galway, Ireland;(3) Department of Radiation Oncology, Duke University School of Medicine, Durham, NC, USA |
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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. |
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