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