Retinoschisin also known as X-linked juvenile retinoschisis protein is a
lectin
Lectins are carbohydrate-binding proteins that are highly specific for sugar Moiety (chemistry), groups that are part of other molecules, so cause agglutination (biology), agglutination of particular cells or precipitation of glycoconjugates an ...
that in humans is encoded by the ''RS1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
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,
as well as in the
pineal gland
The pineal gland (also known as the pineal body or epiphysis cerebri) is a small endocrine gland in the brain of most vertebrates. It produces melatonin, a serotonin-derived hormone, which modulates sleep, sleep patterns following the diurnal c ...
.
Retinoschisin (RS1) is encoded by the gene ''RS1'' located on the X chromosome at ''p22.1''.
Young males who have an ''RS1'' mutation are susceptible to retinoschisis, and X-linked eye disease which causes
macular degeneration
Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred vision, blurred or vision loss, no vision in the center of the visual field. Early on there are often no sym ...
and can lead to a loss of vision.
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.
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.
RS1 also plays a role in the regulation on intracellular MAP kinase signalling.
Structure
The retinoschisin monomer is 224 amino acids long,
including a 23-amino acid signal peptide essential for secretion
(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,
important for the protein's function in cell to cell adhesion. However, its oligomeric structure is a pairing of back-to-back octamers,
forming a homo16me
This structure allows it to adhere to the plasma membrane of retinal cells such as bipolar and photoreceptor cells,
joining them together.
Clinical significance
Pathogenic mutations of this gene are responsible for X-linked
retinoschisis an early-onset
macular degeneration
Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred vision, blurred or vision loss, no vision in the center of the visual field. Early on there are often no sym ...
in males that results in a splitting of the inner layers of the retina and severe loss in vision.
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),
and defective
synapse
In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...
activity.
Retinas that lack mature retinoshisin develop these characteristics in up to 1 in 5,000 males.
There are over 200 mutations of RS1 recorded in th
Retina International Mutation Database, most of which are not pathogenic.
References
Further reading
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External links
GeneReview/NCBI/NIH/UW entry on X-Linked Juvenile Retinoschisis
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