Inositol trisphosphate receptor (InsP3R) is a membrane

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glyco ...

complex acting as a Ca²⁺ channel activated by

inositol trisphosphate Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the p ...

(InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis, fertilization, development, behavior, learning and memory. Inositol triphosphate receptor represents a dominant second messenger leading to the release of Ca²⁺ from intracellular store sites. There is strong evidence suggesting that the InsP3R plays an important role in the conversion of external stimuli to intracellular Ca²⁺ signals characterized by complex patterns relative to both space and time, such as Ca²⁺ waves and oscillations.

Discovery

The InsP3 receptor was first purified from rat cerebellum by neuroscientists Surachai Supattapone and Solomon Snyder at Johns Hopkins University School of Medicine. The cDNA of the InsP3 receptor was first cloned in the laboratory of Katsuhiko Mikoshiba. The initial sequencing was reported as an unknown protein enriched in the cerebellum called P400. The large size of this open reading frame indicated a molecular weight similar to the protein purified biochemically, and soon thereafter it was confirmed that the protein p400 was in fact the inositol trisphosphate receptor.

Distribution

The receptor has a broad tissue distribution but is especially abundant in the

cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebe ...

. Most of the InsP3Rs are found integrated into 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 ...

Structure

The asymmetric structure consists of an N-terminal beta-trefoil domain and a C-terminal

alpha helical 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 ...

domain with a folding pattern similar to an

armadillo repeat An armadillo repeat is the name of a characteristic, repetitive amino acid sequence of about 40 residues in length that is found in many proteins. Proteins that contain armadillo repeats typically contain several tandemly repeated copies. Each ar ...

fold. The split formed by the two terminals contains multiple arginine and lysine residues that coordinate the three phosphoryl groups of InsP3R. The InsP3R complex is formed of four 313 kDa subunits. In amphibians, fish and mammals, there are 3

paralogs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...

and these can form homo- or hetero-oligomers. InsP3R-1 is the most widely expressed of these three and is found in all tissue types and all developmental stages of life. It is additionally the means for further InsP3 receptor diversity in that it has as many as four splice sites with as many as 9 different optional exons or exon variants. Combinations of these can be introduced into a given transcript in order to modulate its pharmacological activity.

References

External links

* {{DEFAULTSORT:Inositol Trisphosphate Receptor Signal transduction Transmembrane receptors Inositol

Discovery

Distribution

Structure

See also

References

External links