Retinoschisin also known as X-linked juvenile retinoschisis protein is a lectin[5][6] that in humans is encoded by the RS1gene.[7]
It is a soluble, cell-surface protein that plays an important role in the maintenance of the retina where it is expressed and secreted by retinal bipolar cells and photoreceptors,[8][9] as well as in the pineal gland.[10] Retinoschisin (RS1) is encoded by the gene RS1 located on the X chromosome at p22.1.[7] Young males who have an RS1 mutation are susceptible to retinoschisis, and X-linked eye disease which causes macular degeneration and can lead to a loss of vision.[5][9]
Function
Retinoschisin is an extracellular protein that plays a crucial role in the cellular organization of the retina: it binds the plasma membranes of various retinal cells tightly to maintain the structure of the retina.[5] In addition to enabling cell-to-cell adhesion, it has been shown that retinoschisin interacts with the sodium/potassium-ATPase (Na/K-ATPase) which resides in the plasma membrane.[10] RS1 also plays a role in the regulation on intracellular MAP kinase signalling.[11]
Structure
The retinoschisin monomer is 224 amino acids long,[7] including a 23-amino acid signal peptide essential for secretion[5] (this is cleaved off before the protein becomes functional), and a highly conserved sequence motif called the discoidin domain which consists of 157 amino acids,[12] important for the protein's function in cell to cell adhesion.[13] However, its oligomeric structure is a pairing of back-to-back octamers,[8] forming a homo16mer [1]. This structure allows it to adhere to the plasma membrane of retinal cells such as bipolar and photoreceptor cells,[9] joining them together.
Clinical significance
Pathogenic mutations of this gene are responsible for X-linked retinoschisis an early-onset macular degeneration in males that results in a splitting of the inner layers of the retina and severe loss in vision.[14] Female carriers of the RS1 mutation do not show symptoms of X-linked juvenile retinoschisis, except in rare cases where the non-functional protein is expressed due to anomalous X-chromosome inactivation. In young males who carry a gene mutation, the disease presents itself as retinal cavities, splitting of inner retinal layers (also known as foveal schisis),[8][5] and defective synapse activity.[5][12] Retinas that lack mature retinoshisin develop these characteristics in up to 1 in 5,000 males.[11] There are over 200 mutations of RS1 recorded in the Retina International Mutation Database, most of which are not pathogenic.
^Weber BH, Kellner U (2007). "X-Linked Juvenile Retinoschisis". In Tombran-Tink J, Barnstable C (eds.). Retinal Degenerations: Biology, Diagnostics, and Therapeutics. Springer Science & Business Media. pp. 119–135. ISBN978-1-59745-186-4.
Alitalo T, Kruse TA, de la Chapelle A (March 1991). "Refined localization of the gene causing X-linked juvenile retinoschisis". Genomics. 9 (3): 505–10. doi:10.1016/0888-7543(91)90417-D. PMID2032721.
Hotta Y, Fujiki K, Hayakawa M, Ohta T, Fujimaki T, Tamaki K, Yokoyama T, Kanai A, Hirakata A, Hida T, Nishina S, Azuma N (August 1998). "Japanese juvenile retinoschisis is caused by mutations of the XLRS1 gene". Human Genetics. 103 (2): 142–4. doi:10.1007/pl00008705. PMID9760195. S2CID23149265.
Shastry BS, Hejtmancik FJ, Trese MT (March 1999). "Recurrent missense (R197C) and nonsense (Y89X) mutations in the XLRS1 gene in families with X-linked retinoschisis". Biochemical and Biophysical Research Communications. 256 (2): 317–9. doi:10.1006/bbrc.1999.0323. PMID10079181.
Gehrig A, White K, Lorenz B, Andrassi M, Clemens S, Weber BH (June 1999). "Assessment of RS1 in X-linked juvenile retinoschisis and sporadic senile retinoschisis". Clinical Genetics. 55 (6): 461–5. doi:10.1034/j.1399-0004.1999.550611.x. PMID10450864. S2CID10619184.
Tuvdendorj D, Isashiki Y, Ohba N, Sonoda S, Izumo S (June 2002). "Two Japanese patients with mutations in the XLRS1 gene". Retina. 22 (3): 354–7. doi:10.1097/00006982-200206000-00017. PMID12055472.
Wistow G, Bernstein SL, Wyatt MK, Ray S, Behal A, Touchman JW, Bouffard G, Smith D, Peterson K (June 2002). "Expressed sequence tag analysis of human retina for the NEIBank Project: retbindin, an abundant, novel retinal cDNA and alternative splicing of other retina-preferred gene transcripts". Molecular Vision. 8: 196–204. PMID12107411.
Inoue Y, Yamamoto S, Inoue T, Fujikado T, Kusaka S, Ohguro N, Ohji M, Tano Y (October 2002). "Two novel point mutations of the XLRS1 gene in patients with X-linked juvenile retinoschisis". American Journal of Ophthalmology. 134 (4): 622–4. doi:10.1016/S0002-9394(02)01592-1. PMID12383832.
Tanimoto N, Usui T, Takagi M, Hasegawa S, Abe H, Sekiya K, Miyagawa Y, Nakazawa M (2003). "Electroretinographic findings in three family members with X-linked juvenile retinoschisis associated with a novel Pro192Thr mutation of the XLRS1 gene". Japanese Journal of Ophthalmology. 46 (5): 568–76. doi:10.1016/S0021-5155(02)00539-7. PMID12457918.
Sato M, Oshika T, Kaji Y, Nose H (2003). "Three novel mutations in the X-linked juvenile retinoschisis (XLRS1) gene in 6 Japanese patients, 1 of whom had Turner's syndrome". Ophthalmic Research. 35 (5): 295–300. doi:10.1159/000072151. PMID12920343. S2CID30631231.
