Synthesis Of Calcium-Off Mechanisms

In 1947, experiments in which small quantities of Ca2+ ions were injected directly into the cell showed that an increase in intracellular calcium led to skeletal contractions. However it was not until the early 1960s when the way calcium ions were stored in cells became clearer thanks to work from Ebashi and Lipmann. (Burgoyne and Petersen, 1997).
Calcium signalling determines whether or not a cell is activated. It is determined by calcium-ON and calcium-OFF mechanisms. Calcium-ON is responsible for pouring Ca2+ into the cytoplasm, from both internal and external sources. The calcium-OFF mechanism however removes cytoplasmic Ca2+ by pumping it out of the cell, or back into the internal stores (Heldin and Purton, 1996).
Source operated calcium entry (SOCE) can be stimulated by iPLA2. iPLA2 is a very interesting phospholipase that does not require Ca2+ for its activation. It is however Ca2+ independent, which allows it to function properly in the presence of strong Ca2+ chelators. (Jenkins C. et al, 2001) One of the main features of this molecule is that is contains CaM-binding domain in the C-terminus which, along with the IQ motif, forms a pocket, enabling CaM to bind and inhibit iPLA2β activity (Wolf M., Gross R., 1996)
Stromal interaction molecule 1
Unlike before, this paper explains how they are important, and how the inhibition of iPLA2 impairs SOCE. This had previously not been done in papers before this one and so therefore taught us something about the SOCE mechanism and the signalling pathways that regulate it. STIM1 also has a key role to play in this particular research paper, showing that it too plays a role in SOCE by mediating agonist induced calcium entry (ACE). Previously, ACE was thought to only have been regulated by one signalling pathway, this research paper suggests that there a multiple non-related pathways in iPLA2 and