Nyctalopin is a protein located on the surface of photoreceptor-to-ON bipolar cell synapse in the retina. It is composed of 481 amino acids.[1] and is encoded in human by the NYXgene.[2][3][4] This gene is found on the chromosome X[5] and has two exons.[1] This protein is a leucine-rich proteoglycan[6] which is expressed in the eye, spleen and brain in mice.[7]Mutations in this gene cause congenital stationary night blindness in humans (CSNB).[8] which is a stable retinal disorder.[2] The consequence of this mutation results in an abnormal night vision. Nyctalopin is critical due to the fact that it generates a depolarizing bipolar cell response due to the mutation on the NYX gene.[6] Most of the time, CSNB are associated to hygh myopia which is the result of a mutation on the same gene.[1] Several mutations can occur on the NYX gene resulting on many form of night blindness in humans.[1] Some studies show that these mutations are more present in Asian population than in Caucasian population.[1] A mouse strain called nob (no b-wave) carries a spontaneous mutation leading to a frameshift in this gene. These mice are used as an animal model for congenital stationary night blindness.[9]
The first evidence of the existence of mutation in NYX gene, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness was provided by Richard G. Weleber at the University of Alberta in 2000.[2]
Nyctalopin contains a N-terminal signal peptide and a C-terminal glycosylphosphatidylinositol (GPI) anchor.[15] Predicted signal sequence is likely to be processed by a co-translational mechanism.[16] Nyctalopin does not have two transmembrane domains and the only transmembrane domain is found to be between the amino acid 452 ad 472.[16] In the endoplasmic reticulum, the protein is oriented with the N-terminus in the lumen of the endoplasmic reticulum and the C-terminus is located in the cytoplasm.[16] The central part of the polypeptide encodes 11 consecutive leucines-rich repeats (LRRs).[3] These LRR are flanked by N-terminal and C-terminal rich LRRs[3] Tandem LRRs domains are folded into ß-sheets and α-helices, all joined by loops.[16] According to the cysteine pattern, nyctalopin is part of the class II small leucine-rich proteoglycans.[3] These proteins, are involved in several functions such as cell signalling, growth control, and formation of the extracellular matrix.[3] LRR domains are involved in the protein–protein interaction in small leucine rich repeat proteoglycan family members.[15] Also, LRR domains have a critical role in nyctalopin function. Congenital stationary night blindness in humans appears when a mutation in the LRR domains of nyctalopin occurs.
The complete form of congenital stationary night blindness is due to the absence of nyctalopin.[16] This absence is due to a mutation involving an 85 base pair deletion.[17] In humans, more than 30 mutations are found in the NYX gene and most of them have an impact either on the tertiary structure of the LRR domains of nyctalopin or to truncate the protein.[15]
^ abcBech-Hansen NT, Naylor MJ, Maybaum TA, Sparkes RL, Koop B, Birch DG, Bergen AA, Prinsen CF, Polomeno RC, Gal A, Drack AV, Musarella MA, Jacobson SG, Young RS, Weleber RG (November 2000). "Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness". Nature Genetics. 26 (3): 319–23. doi:10.1038/81619. PMID11062471. S2CID10223880.
^ abcdePusch CM, Zeitz C, Brandau O, Pesch K, Achatz H, Feil S, Scharfe C, Maurer J, Jacobi FK, Pinckers A, Andreasson S, Hardcastle A, Wissinger B, Berger W, Meindl A (November 2000). "The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein". Nature Genetics. 26 (3): 324–7. doi:10.1038/81627. PMID11062472. S2CID42428370.
^Jacobi FK, Andréasson S, Langrova H, Meindl A, Zrenner E, Apfelstedt-Sylla E, Pusch CM (October 2002). "Phenotypic expression of the complete type of X-linked congenital stationary night blindness in patients with different mutations in the NYX gene". Graefe's Archive for Clinical and Experimental Ophthalmology. 240 (10): 822–8. doi:10.1007/s00417-002-0562-z. PMID12397430. S2CID25140284.
Musarella MA, Weleber RG, Murphey WH, Young RS, Anson-Cartwright L, Mets M, Kraft SP, Polemeno R, Litt M, Worton RG (November 1989). "Assignment of the gene for complete X-linked congenital stationary night blindness (CSNB1) to Xp11.3". Genomics. 5 (4): 727–37. doi:10.1016/0888-7543(89)90114-6. PMID2574143.
Hardcastle AJ, David-Gray ZK, Jay M, Bird AC, Bhattacharya SS (December 1997). "Localization of CSNBX (CSNB4) between the retinitis pigmentosa loci RP2 and RP3 on proximal Xp". Investigative Ophthalmology & Visual Science. 38 (13): 2750–5. PMID9418727.
Jacobi FK, Andréasson S, Langrova H, Meindl A, Zrenner E, Apfelstedt-Sylla E, Pusch CM (October 2002). "Phenotypic expression of the complete type of X-linked congenital stationary night blindness in patients with different mutations in the NYX gene". Graefe's Archive for Clinical and Experimental Ophthalmology. 240 (10): 822–8. doi:10.1007/s00417-002-0562-z. PMID12397430. S2CID25140284.
Zito I, Allen LE, Patel RJ, Meindl A, Bradshaw K, Yates JR, Bird AC, Erskine L, Cheetham ME, Webster AR, Poopalasundaram S, Moore AT, Trump D, Hardcastle AJ (February 2003). "Mutations in the CACNA1F and NYX genes in British CSNBX families". Human Mutation. 21 (2): 169. doi:10.1002/humu.9106. PMID12552565. S2CID13143864.
Khan NW, Kondo M, Hiriyanna KT, Jamison JA, Bush RA, Sieving PA (January 2005). "Primate Retinal Signaling Pathways: Suppressing ON-Pathway Activity in Monkey With Glutamate Analogues Mimics Human CSNB1-NYX Genetic Night Blindness". Journal of Neurophysiology. 93 (1): 481–92. doi:10.1152/jn.00365.2004. PMID15331616.
Zeitz C, Minotti R, Feil S, Mátyás G, Cremers FP, Hoyng CB, Berger W (March 2005). "Novel mutations in CACNA1F and NYX in Dutch families with X-linked congenital stationary night blindness". Molecular Vision. 11: 179–83. PMID15761389.
