1. Function

2. Clinical significance

3. Structure

4. References

5. Further reading

6. External links

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,^[4][5] as well as in the pineal gland.^[6] Retinoschisin (RS1) is encoded by the gene RS1 located on the X chromosome at p22.1.^[3] 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.^[1][5]

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.^[1] 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.^[6] RS1 also plays a role in the regulation on intracellular MAP kinase signalling.^[7]

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.^[8] 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),^[4][1] and defective synapse activity.^[1][9] Retinas that lack mature retinoshisin develop these characteristics in up to 1 in 5,000 males.^[7] There are over 200 mutations of RS1 recorded in the Retina International Mutation Database, most of which are not pathogenic.

Structure

The retinoschisin monomer is 224 amino acids long,^[3] including a 23-amino acid signal peptide essential for secretion^[1] (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,^[9] important for the protein's function in cell to cell adhesion.^[10] However, its oligomeric structure is a pairing of back-to-back octamers,^[4] forming a homo16mer [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147653]. This structure allows it to adhere to the plasma membrane of retinal cells such as bipolar and photoreceptor cells,^[5] joining them together.

References

Further reading

• {{cite journal | vauthors = Sikkink SK, Biswas S, Parry NR, Stanga PE, Trump D | title = X-linked retinoschisis: an update | journal = Journal of Medical Genetics | volume = 44 | issue = 4 | pages = 225–32 | date = April 2007 | pmid = 17172462 | pmc = 2598044 | doi = 10.1136/jmg.2006.047340 }}
• {{cite journal | vauthors = Alitalo T, Kruse TA, de la Chapelle A | title = Refined localization of the gene causing X-linked juvenile retinoschisis | journal = Genomics | volume = 9 | issue = 3 | pages = 505–10 | date = March 1991 | pmid = 2032721 | doi = 10.1016/0888-7543(91)90417-D }}
• {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = September 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 }}
• {{cite journal | vauthors = Hotta Y, Fujiki K, Hayakawa M, Ohta T, Fujimaki T, Tamaki K, Yokoyama T, Kanai A, Hirakata A, Hida T, Nishina S, Azuma N | title = Japanese juvenile retinoschisis is caused by mutations of the XLRS1 gene | journal = Human Genetics | volume = 103 | issue = 2 | pages = 142–4 | date = August 1998 | pmid = 9760195 | doi = 10.1007/pl00008705 }}
• {{cite journal | vauthors = Shastry BS, Hejtmancik FJ, Trese MT | title = Recurrent missense (R197C) and nonsense (Y89X) mutations in the XLRS1 gene in families with X-linked retinoschisis | journal = Biochemical and Biophysical Research Communications | volume = 256 | issue = 2 | pages = 317–9 | date = March 1999 | pmid = 10079181 | doi = 10.1006/bbrc.1999.0323 }}
• {{cite journal | vauthors = Mashima Y, Shinoda K, Ishida S, Ozawa Y, Kudoh J, Iwata T, Oguchi Y, Shimizu N | title = Identification of four novel mutations of the XLRS1 gene in Japanese patients with X-linked juvenile retinoschisis. Mutation in brief no. 234. Online | journal = Human Mutation | volume = 13 | issue = 4 | pages = 338 | year = 1999 | pmid = 10220153 | doi = 10.1002/(SICI)1098-1004(1999)13:4<338::AID-HUMU16>3.0.CO;2-0 }}
• {{cite journal | vauthors = Huopaniemi L, Rantala A, Forsius H, Somer M, de la Chapelle A, Alitalo T | title = Three widespread founder mutations contribute to high incidence of X-linked juvenile retinoschisis in Finland | journal = European Journal of Human Genetics | volume = 7 | issue = 3 | pages = 368–76 | date = April 1999 | pmid = 10234514 | doi = 10.1038/sj.ejhg.5200300 }}
• {{cite journal | vauthors = Gehrig A, White K, Lorenz B, Andrassi M, Clemens S, Weber BH | title = Assessment of RS1 in X-linked juvenile retinoschisis and sporadic senile retinoschisis | journal = Clinical Genetics | volume = 55 | issue = 6 | pages = 461–5 | date = June 1999 | pmid = 10450864 | doi = 10.1034/j.1399-0004.1999.550611.x }}
• {{cite journal | vauthors = Hiriyanna KT, Bingham EL, Yashar BM, Ayyagari R, Fishman G, Small KW, Weinberg DV, Weleber RG, Lewis RA, Andreasson S, Richards JE, Sieving PA | title = Novel mutations in XLRS1 causing retinoschisis, including first evidence of putative leader sequence change | journal = Human Mutation | volume = 14 | issue = 5 | pages = 423–7 | year = 2000 | pmid = 10533068 | doi = 10.1002/(SICI)1098-1004(199911)14:5<423::AID-HUMU8>3.0.CO;2-D }}
• {{cite journal | vauthors = Grayson C, Reid SN, Ellis JA, Rutherford A, Sowden JC, Yates JR, Farber DB, Trump D | title = Retinoschisin, the X-linked retinoschisis protein, is a secreted photoreceptor protein, and is expressed and released by Weri-Rb1 cells | journal = Human Molecular Genetics | volume = 9 | issue = 12 | pages = 1873–9 | date = July 2000 | pmid = 10915776 | doi = 10.1093/hmg/9.12.1873 }}
• {{cite journal | vauthors = Weber BH, Schrewe H, Molday LL, Gehrig A, White KL, Seeliger MW, Jaissle GB, Friedburg C, Tamm E, Molday RS | title = Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organization and synaptic structure | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 9 | pages = 6222–7 | date = April 2002 | pmid = 11983912 | pmc = 122930 | doi = 10.1073/pnas.092528599 }}
• {{cite journal | vauthors = Tuvdendorj D, Isashiki Y, Ohba N, Sonoda S, Izumo S | title = Two Japanese patients with mutations in the XLRS1 gene | journal = Retina | volume = 22 | issue = 3 | pages = 354–7 | date = June 2002 | pmid = 12055472 | doi = 10.1097/00006982-200206000-00017 }}
• {{cite journal | vauthors = Wistow G, Bernstein SL, Wyatt MK, Ray S, Behal A, Touchman JW, Bouffard G, Smith D, Peterson K | title = 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 | journal = Molecular Vision | volume = 8 | issue = | pages = 196–204 | date = June 2002 | pmid = 12107411 | doi = }}
• {{cite journal | vauthors = Inoue Y, Yamamoto S, Inoue T, Fujikado T, Kusaka S, Ohguro N, Ohji M, Tano Y | title = Two novel point mutations of the XLRS1 gene in patients with X-linked juvenile retinoschisis | journal = American Journal of Ophthalmology | volume = 134 | issue = 4 | pages = 622–4 | date = October 2002 | pmid = 12383832 | doi = 10.1016/S0002-9394(02)01592-1 }}
• {{cite journal | vauthors = Wang T, Waters CT, Rothman AM, Jakins TJ, Römisch K, Trump D | title = Intracellular retention of mutant retinoschisin is the pathological mechanism underlying X-linked retinoschisis | journal = Human Molecular Genetics | volume = 11 | issue = 24 | pages = 3097–105 | date = November 2002 | pmid = 12417531 | doi = 10.1093/hmg/11.24.3097 }}
• {{cite journal | vauthors = Tanimoto N, Usui T, Takagi M, Hasegawa S, Abe H, Sekiya K, Miyagawa Y, Nakazawa M | title = Electroretinographic findings in three family members with X-linked juvenile retinoschisis associated with a novel Pro192Thr mutation of the XLRS1 gene | journal = Japanese Journal of Ophthalmology | volume = 46 | issue = 5 | pages = 568–76 | year = 2003 | pmid = 12457918 | doi = 10.1016/S0021-5155(02)00539-7 }}
• {{cite journal | vauthors = Fraternali F, Cavallo L, Musco G | title = Effects of pathological mutations on the stability of a conserved amino acid triad in retinoschisin | journal = FEBS Letters | volume = 544 | issue = 1-3 | pages = 21–6 | date = June 2003 | pmid = 12782284 | doi = 10.1016/S0014-5793(03)00433-2 }}
• {{cite journal | vauthors = Sato M, Oshika T, Kaji Y, Nose H | title = Three novel mutations in the X-linked juvenile retinoschisis (XLRS1) gene in 6 Japanese patients, 1 of whom had Turner's syndrome | journal = Ophthalmic Research | volume = 35 | issue = 5 | pages = 295–300 | year = 2003 | pmid = 12920343 | doi = 10.1159/000072151 }}

External links

• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=retinoschisis GeneReview/NCBI/NIH/UW entry on X-Linked Juvenile Retinoschisis]

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