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Current Topics in Biochemical Research   Volumes    Volume 2 
Abstract
Regulation of type I Ip3receptors and neurodegeneration
Lise Sofie Haug, Anne Carine Østvold
Pages: 77 - 89
Number of pages: 13
Current Topics in Biochemical Research
Volume 2 

Copyright © 2000 Research Trends. All rights reserved

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.

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