Inositol trisphosphate receptor (InsP3R) is a membrane

glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) 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 a ...

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 ...

(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 In molecular biology, reading frames are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible reading frames ...

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 (: cerebella or cerebellums; 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 it or eve ...

. Most of the InsP3Rs are found integrated into the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

Structure

Several X-ray crystallographic and electron cryomicroscopic (cryo-EM) structures of IP₃Rs from mouse, rat, and human have defined the overall architecture of the channel. The 1.2 MDa C4-symmetric assembly consists of an ER-embedded transmembrane domain (TMD) in a domain-swapped 6 transmembrane (6TM) cation channel fold that is capped by a large cytosolic domain (CD). In this manner, IP₃Rs share significant homology with the much larger and distantly-related RyRs. The CD contains all known ligand binding sites, including the IP₃ binding site, two Ca²⁺ binding sites, an adenine nucleotide binding site, and a C₂H₂ Zn²⁺ finger fold. A comprehensive Ca²⁺-dependent conformational landscape has been defined by cryo-EM.

References

External links

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

Discovery

Distribution

Structure

See also

References

External links