ABSTRACT

The inositol (1,4,5)-trisphosphate (IP₃)¹ receptor is an intracellular  Ca²⁺ Channel localised to the endoplasmic reticulum (ER), which releases Ca²⁺ in response to binding of the plasma membrane-derived, soluble second messenger, IP₃. Sequestration of Ca²⁺ into intracellular storage compartments like the ER takes place in all cells, and is necessary due to the importance of Ca²⁺ as a messenger molecule. IP₃ receptors are found in virtually all cell types studied, but the three isoforms exhibit differences in molecular properties, tissue distribution and regulation. Further diversibility is provided by alternative splicing of IP₃ receptor mRNA. The longest form of the type I IP₃ receptor is found exclusively in neurons. Where it plays a major role in the regulation of intracellular calcium homeostasis.

Maintenance of intracellular calcium homeostasis is of crucial importance in eukaryotic cells, and  increased calcium concentrations will quickly lead to irreversible damage and eventually to cell death by apoptosis. The type I IP₃ receptor protein and its calcium channel activity may be regulated in various ways. In this review we discuss the phosphorylation of the type I IP3 receptor by different protein kinases, and the proteolytic degradation y different proteases under certain conditions. Increasing evidence supporting the notion that decreased levels IP₃ receptors participate in the development of neurodegenerative conditions is discussed.