The inositol 1,4,5-trisphosphate receptor (IP3R) is expressed at very high levels in cerebellar Purkinje cells. Within these neurons, it has a widespread distribution throughout the endoplasmic reticulum (ER) and is present at particularly high concentrations at sites of membrane appositions within peculiar stacks of ER cisternae. Here we report that stacks of ER cisternae, reminiscent of those observed in Purkinje cells, can be induced by overexpression of full-length IPA, but not of mutant forms of the protein in COS cells. Within these stacks the IP3R forms a crystalline array at apposed cisternal faces. Additionally, we show that Purkinje cell stacks are not permanent structures. Our findings suggest that massive stack formation in Purkinje cells represents an adaptive response of the ER to hypoxic conditions and is due to the presence of the high concentration of IP3R in its membranes.
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