Retinoschisin

Last updated
RS1
3jd6.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases RS1 , RS, XLretinoschisin 1
External IDs OMIM: 300839 MGI: 1336189 HomoloGene: 279 GeneCards: RS1
Orthologs
SpeciesHumanMouse
Entrez

6247

20147

Ensembl

ENSG00000102104

ENSMUSG00000031293

UniProt

O15537

Q9Z1L4

RefSeq (mRNA)

NM_000330

NM_011302

RefSeq (protein)

NP_000321

NP_035432

Location (UCSC) Chr X: 18.64 – 18.67 Mb Chr X: 159.55 – 159.58 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Retinoschisin also known as X-linked juvenile retinoschisis protein is a lectin [5] [6] that in humans is encoded by the RS1 gene. [7]

Contents

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 . 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.

Related Research Articles

<span class="mw-page-title-main">Retinitis pigmentosa</span> Gradual retinal degeneration leading to progressive sight loss

Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision. As peripheral vision worsens, people may experience "tunnel vision". Complete blindness is uncommon. Onset of symptoms is generally gradual and often begins in childhood.

<span class="mw-page-title-main">Retinoschisis</span> Eye disease involving splitting of the retina

Retinoschisis is an eye disease characterized by the abnormal splitting of the retina's neurosensory layers, usually in the outer plexiform layer. Retinoschisis can be divided into degenerative forms which are very common and almost exclusively involve the peripheral retina and hereditary forms which are rare and involve the central retina and sometimes the peripheral retina. The degenerative forms are asymptomatic and involve the peripheral retina only and do not affect the visual acuity. Some rarer forms result in a loss of vision in the corresponding visual field.

<span class="mw-page-title-main">Congenital stationary night blindness</span> Medical condition

Congenital stationary night blindness (CSNB) is a rare non-progressive retinal disorder. People with CSNB often have difficulty adapting to low light situations due to impaired photoreceptor transmission. These patients may also have reduced visual acuity, myopia, nystagmus, and strabismus. CSNB has two forms -- complete, also known as type-1 (CSNB1), and incomplete, also known as type-2 (CSNB2), which are distinguished by the involvement of different retinal pathways. In CSNB1, downstream neurons called bipolar cells are unable to detect neurotransmission from photoreceptor cells. CSNB1 can be caused by mutations in various genes involved in neurotransmitter detection, including NYX. In CSNB2, the photoreceptors themselves have impaired neurotransmission function; this is caused primarily by mutations in the gene CACNA1F, which encodes a voltage-gated calcium channel important for neurotransmitter release. CSNB has been identified in horses and dogs as the result of mutations in TRPM1, GRM6, and LRIT3 .

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<span class="mw-page-title-main">Photoreceptor cell-specific nuclear receptor</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Retinitis pigmentosa GTPase regulator</span> Protein-coding gene in the species Homo sapiens

X-linked retinitis pigmentosa GTPase regulator is a GTPase-binding protein that in humans is encoded by the RPGR gene. The gene is located on the X-chromosome and is commonly associated with X-linked retinitis pigmentosa (XLRP). In photoreceptor cells, RPGR is localized in the connecting cilium which connects the protein-synthesizing inner segment to the photosensitive outer segment and is involved in the modulation of cargo trafficked between the two segments.

<span class="mw-page-title-main">ABCA4</span> Mammalian protein found in Homo sapiens

ATP-binding cassette, sub-family A (ABC1), member 4, also known as ABCA4 or ABCR, is a protein which in humans is encoded by the ABCA4 gene.

<span class="mw-page-title-main">Peripherin 2</span> Protein-coding gene in the species Homo sapiens

Peripherin-2 is a protein, that in humans is encoded by the PRPH2 gene. Peripherin-2 is found in the rod and cone cells of the retina of the eye. Defects in this protein result in one form of retinitis pigmentosa, an incurable blindness.

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<i>CRX</i> (gene) Protein-coding gene in the species Homo sapiens

Cone-rod homeobox protein is a protein that in humans is encoded by the CRX gene.

<span class="mw-page-title-main">Retinaldehyde-binding protein 1</span> Protein-coding gene in the species Homo sapiens

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<i>NRL</i> (gene) Protein-coding gene in the species Homo sapiens

Neural retina-specific leucine zipper protein is a protein that in humans is encoded by the NRL gene.

<span class="mw-page-title-main">Orthodenticle homeobox 2</span> Protein-coding gene in the species Homo sapiens

Homeobox protein OTX2 is a protein that in humans is encoded by the OTX2 gene.

<span class="mw-page-title-main">Nyctalopin</span> Protein-coding gene in the species Homo sapiens

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. and is encoded in human by the NYX gene. This gene is found on the chromosome X and has two exons. This protein is a leucine-rich proteoglycan which is expressed in the eye, spleen and brain in mice. Mutations in this gene cause congenital stationary night blindness in humans (CSNB). which is a stable retinal disorder. 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. Most of the time, CSNB are associated to hygh myopia which is the result of a mutation on the same gene. Several mutations can occur on the NYX gene resulting on many form of night blindness in humans. Some studies show that these mutations are more present in Asian population than in Caucasian population. A mouse strain called nob carries a spontaneous mutation leading to a frameshift in this gene. These mice are used as an animal model for congenital stationary night blindness.

<span class="mw-page-title-main">POMT1</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">ROM1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">RP1</span> Protein-coding gene in humans

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<span class="mw-page-title-main">Retinal degeneration (rhodopsin mutation)</span> Retinopathy

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<span class="mw-page-title-main">Paul A. Sieving</span>

Paul A. Sieving is a former director of the National Eye Institute, part of the U.S. National Institutes of Health. Prior to joining the NIH in 2001, he served on the faculty of the University of Michigan Medical School as the Paul R. Lichter Professor of Ophthalmic Genetics. He also was the founding director of the Center for Retinal and Macular Degeneration in the university's Department of Ophthalmology and Visual Sciences. 

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000102104 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031293 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 4 5 6 Vijayasarathy C, Ziccardi L, Sieving PA (2012). "Biology of Retinoschisin". Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology. Vol. 723. pp. 513–8. doi:10.1007/978-1-4614-0631-0_64. ISBN   978-1-4614-0630-3. PMC   3475158 . PMID   22183371.
  6. ↑ Wu WW (October 2005). RS1 structure-function relationships: roles in retinal adhesion and X-linked retinoschisis (Ph.D. thesis). The University of British Columbia.
  7. 1 2 3 Sauer CG, Gehrig A, Warneke-Wittstock R, Marquardt A, Ewing CC, Gibson A, Lorenz B, Jurklies B, Weber BH (October 1997). "Positional cloning of the gene associated with X-linked juvenile retinoschisis". Nature Genetics. 17 (2): 164–70. doi:10.1038/ng1097-164. PMID   9326935. S2CID   7829510.
  8. 1 2 3 Tolun G, Vijayasarathy C, Huang R, Zeng Y, Li Y, Steven AC, Sieving PA, Heymann JB (May 2016). "Paired octamer rings of retinoschisin suggest a junctional model for cell-cell adhesion in the retina". Proceedings of the National Academy of Sciences of the United States of America. 113 (19): 5287–92. Bibcode:2016PNAS..113.5287T. doi: 10.1073/pnas.1519048113 . PMC   4868477 . PMID   27114531.
  9. 1 2 3 Kotova S, Vijayasarathy C, Dimitriadis EK, Ikonomou L, Jaffe H, Sieving PA (August 2010). "Retinoschisin (RS1) interacts with negatively charged lipid bilayers in the presence of Ca2+: an atomic force microscopy study". Biochemistry. 49 (33): 7023–32. doi:10.1021/bi1007029. PMC   2929131 . PMID   20677810.
  10. 1 2 Plössl K, Royer M, Bernklau S, Tavraz NN, Friedrich T, Wild J, Weber BH, Friedrich U (August 2017). "Retinoschisin is linked to retinal Na/K-ATPase signaling and localization". Molecular Biology of the Cell. 28 (16): 2178–2189. doi:10.1091/mbc.e17-01-0064. PMC   5531734 . PMID   28615319.
  11. 1 2 Plössl K, Schmid V, Straub K, Schmid C, Ammon M, Merkl R, Weber BH, Friedrich U (July 2018). "Pathomechanism of mutated and secreted retinoschisin in X-linked juvenile retinoschisis". Experimental Eye Research. 177: 23–34. doi:10.1016/j.exer.2018.07.021. PMID   30040949. S2CID   51717282.
  12. 1 2 Reid SN, Yamashita C, Farber DB (July 2003). "Retinoschisin, a photoreceptor-secreted protein, and its interaction with bipolar and muller cells". The Journal of Neuroscience. 23 (14): 6030–40. doi:10.1523/JNEUROSCI.23-14-06030.2003. PMC   6740352 . PMID   12853421.
  13. ↑ Wu WW, Molday RS (July 2003). "Defective discoidin domain structure, subunit assembly, and endoplasmic reticulum processing of retinoschisin are primary mechanisms responsible for X-linked retinoschisis". The Journal of Biological Chemistry. 278 (30): 28139–46. doi: 10.1074/jbc.M302464200 . PMID   12746437.
  14. ↑ 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. ISBN   978-1-59745-186-4.

Further reading

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