Nyctalopin is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

located on the surface of photoreceptor-to-ON bipolar cell synapse in the

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...

. It is composed of 481

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s. and is encoded in human by the ''NYX''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. This gene is found on the

chromosome X The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...

and has two

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

s. This protein is a

leucine Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- ca ...

-rich

proteoglycan Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to whic ...

which is expressed in the eye, spleen and brain in mice.

Mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

s in this gene cause

congenital stationary night blindness 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 visua ...

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 In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is esse ...

bipolar cell response due to the mutation on the ''NYX'' gene. Most of the time, CSNB are associated to hygh

myopia Near-sightedness, also known as myopia and short-sightedness, is an eye disease where light focuses in front of, instead of on, the retina. As a result, distant objects appear blurry while close objects appear normal. Other symptoms may include ...

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 (no b-wave) carries a spontaneous mutation leading to a

frameshift Ribosomal frameshifting, also known as translational frameshifting or translational recoding, is a biological phenomenon that occurs during translation that results in the production of multiple, unique proteins from a single mRNA. The process can ...

in this gene. These mice are used as an

animal model An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...

for congenital stationary night blindness.

Discovery

The first evidence of the existence of mutation in ''NYX'' gene, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness was provided by Richard G. Weleber at the

University of Alberta The University of Alberta, also known as U of A or UAlberta, is a public research university located in Edmonton, Alberta, Canada. It was founded in 1908 by Alexander Cameron Rutherford,"A Gentleman of Strathcona – Alexander Cameron Rutherfor ...

in 2000.

Gene location

The ''NYX'' gene is located on the short arm (p) of chromosome X, from base pair 41,447,434 to base pair 41,475,710.

Protein structure

Nyctalopin contains a N-terminal signal peptide and a C-terminal glycosylphosphatidylinositol (GPI) anchor. Predicted signal sequence is likely to be processed by a co-translational mechanism. Nyctalopin does not have two

transmembrane domain A transmembrane domain (TMD) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. Because the interior of the lipid bil ...

s and the only transmembrane domain is found to be between the amino acid 452 ad 472. In the

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

, the protein is oriented with the N-terminus in the lumen of the endoplasmic reticulum and the C-terminus is located in the cytoplasm. The central part of the

polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

encodes 11 consecutive leucines-rich repeats (LRRs). These LRR are flanked by N-terminal and C-terminal rich LRRs Tandem LRRs domains are folded into ß-sheets and

α-helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ear ...

, all joined by loops. According to the cysteine pattern, nyctalopin is part of the

class II small leucine-rich proteoglycans Class or The Class may refer to: Common uses not otherwise categorized * Class (biology), a taxonomic rank * Class (knowledge representation), a collection of individuals or objects * Class (philosophy), an analytical concept used differently ...

. These proteins, are involved in several functions such as

cell signalling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...

, growth control, and formation of the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...

. LRR domains are involved in the

protein–protein interaction Protein–protein interactions (PPIs) are physical contacts of high specificity established between two or more protein molecules as a result of biochemical events steered by interactions that include electrostatic forces, hydrogen bonding and th ...

in small leucine rich repeat proteoglycan family members. Also, LRR domains have a critical role in nyctalopin function. Congenital stationary night blindness in humans appears when a mutation in the LRR domains of nyctalopin occurs.

Mutations

The complete form of congenital stationary night blindness is due to the absence of nyctalopin. This absence is due to a mutation involving an 85 base pair deletion. In humans, more than 30 mutations are found in the NYX gene and most of them have an impact either on the

tertiary structure Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may int ...

of the LRR domains of nyctalopin or to

truncate In mathematics and computer science, truncation is limiting the number of digits right of the decimal point. Truncation and floor function Truncation of positive real numbers can be done using the floor function. Given a number x \in \mathbb ...

the protein.

References

External links