Inositol trisphosphate receptor

Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as Ca2+ channel activated by inositol trisphosphate (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. For example, Ca2+ waves and oscillations. The InsP3 receptor was first purified from rat cerebellum.

Distribution
It has a broad tissue distribution but is especially abundant in the cerebellum. Most of the InsP3Rs are found in the cell integrated into the endoplasmic reticulum.

Structure
The asymmetric structure consists of an N-terminal beta-trefoil domain and a C-terminal alpha helical domain with a folding pattern similar to an armadillo repeat 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 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.