Biology:Retinoschisin

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


Retinoschisin also known as X-linked juvenile retinoschisis protein is a lectin[1][2] that in humans is encoded by the RS1 gene.[3]

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]

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,[8] important for the protein's function in cell to cell adhesion.[9] However, its oligomeric structure is a pairing of back-to-back octamers,[4] forming a homo16mer [1]. This structure allows it to adhere to the plasma membrane of retinal cells such as bipolar and photoreceptor cells,[5] 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.[10] 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][8] 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.

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 "Biology of retinoschisin". Advances in Experimental Medicine and Biology 723: 513–8. 2012. doi:10.1007/978-1-4614-0631-0_64. ISBN 978-1-4614-0630-3. PMID 22183371. 
  2. Wu WW (October 2005). RS1 structure-function relationships: roles in retinal adhesion and X-linked retinoschisis (Ph.D. thesis). The University of British Columbia.
  3. 3.0 3.1 3.2 "Positional cloning of the gene associated with X-linked juvenile retinoschisis". Nature Genetics 17 (2): 164–70. October 1997. doi:10.1038/ng1097-164. PMID 9326935. 
  4. 4.0 4.1 4.2 "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. May 2016. doi:10.1073/pnas.1519048113. PMID 27114531. Bibcode2016PNAS..113.5287T. 
  5. 5.0 5.1 5.2 "Retinoschisin (RS1) interacts with negatively charged lipid bilayers in the presence of Ca2+: an atomic force microscopy study". Biochemistry 49 (33): 7023–32. August 2010. doi:10.1021/bi1007029. PMID 20677810. 
  6. 6.0 6.1 "Retinoschisin is linked to retinal Na/K-ATPase signaling and localization". Molecular Biology of the Cell 28 (16): 2178–2189. August 2017. doi:10.1091/mbc.e17-01-0064. PMID 28615319. 
  7. 7.0 7.1 "Pathomechanism of mutated and secreted retinoschisin in X-linked juvenile retinoschisis". Experimental Eye Research 177: 23–34. July 2018. doi:10.1016/j.exer.2018.07.021. PMID 30040949. 
  8. 8.0 8.1 "Retinoschisin, a photoreceptor-secreted protein, and its interaction with bipolar and muller cells". The Journal of Neuroscience 23 (14): 6030–40. July 2003. doi:10.1523/JNEUROSCI.23-14-06030.2003. PMID 12853421. 
  9. "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. July 2003. doi:10.1074/jbc.M302464200. PMID 12746437. 
  10. "X-Linked Juvenile Retinoschisis". Retinal Degenerations: Biology, Diagnostics, and Therapeutics. Springer Science & Business Media. 2007. pp. 119–135. ISBN 978-1-59745-186-4. 

Further reading

External links

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