Human Molecular Genetics Advance Access published online on May 19, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi194
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1 Academic Unit of Medical Genetics, School of Medicine and Centre for Molecular Medicine, Faculty of Medical and Human Sciences, University of Manchester
* To whom correspondence should be addressed. Mutations in the gene NYX, which encodes nyctalopin, lead to the retinal disorder congenital stationary night blindness which is characterised by defective night vision (nyctalopia) from birth. Nyctalopin is of unknown function but is predicted to be a secreted glycoprotein of the extracellular small leucine-rich repeat proteoglycan and protein (SLRP) family attached to the cell membrane in humans via a glycosylphosphatidylinositol (GPI) anchor but in mouse via a transmembrane domain. We investigated membrane association and attachment for human and mouse nyctalopin and show conclusively that human nyctalopin is a GPI anchored protein. Furthermore, the orthologous mouse protein, although it localises to the cell surface, is not GPI anchored. We also confirm both mouse and human nyctalopin are glycosylated. Further sequence analysis suggests chimp, dog and frog nyctalopin are likely to be GPI anchored but that rat is not. This is the first reported example of orthologous proteins which have different mechanisms of cell membrane attachment. Notably, the disease causing mutations that have been identified to date in the human NYX gene are all distributed throughout the core LRR region and not in the C-terminal GPI anchor signal sequence. We propose that the presence of nyctalopin on the surface of the cell rather than the mechanism of anchoring is crucial to its function.
Received March 18, 2005
Revised May 11, 2005
Accepted May 11, 2005
Article
Species Specific Membrane Anchoring of Nyctalopin, a Small Leucine Rich Repeat Protein
2 Bioinformatics Group, Institute of Molecular Pathology, Vienna
3 Faculty of Life Sciences, The Michael Smith Building, University of Manchester
4 Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences and Academic Unit of Eye & Vision Science, School of Medicine, University of Manchester
Dorothy Trump, E-mail: dorothy.trump{at}manchester.ac.uk
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