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; OMA:RS1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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, an 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 Archived 2020-01-23 at the Wayback Machine , most of which are not pathogenic.

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

This article incorporates text from the United States National Library of Medicine, which is in the public domain.