Evidence that type I, II, and III inositol 1,4,5-trisphosphate receptors can occur as integral plasma membrane proteins

A number of previous reports have suggested that inositol 1,4,5-trisphospha te receptors (IP(3)Rs) are present in the plasma membranes of cells. We con firm this directly in the present study by demonstrating that a significant proportion of the IP,Rs found in A431 cells, Jurkat cells, and rat parotid acini can be biotinylated by the extracellular application of sulfo-N-hydr oxysuccinimide-biotin to intact cells. This labeling cannot be accounted fo r by the reaction of sulfo-N-hydroxysuccinimide-biotin with intracellular I P(3)Rs since calnexin and the SERCA2 ATPase, both integral membrane protein s of the endoplasmic reticulum, are not labeled under the same experimental conditions. individual IP3R subtypes were detected using subtype-specific antibodies. A431 cells expressed only the type-3 IP3R, and 23% of this prot ein was in the biotinylated (plasma membrane) fraction. Jurkat cells and ra t parotid cells expressed all three IP3R subtypes. Contrary to earlier resu lts suggesting that only the type-3 IP3R might localize to the plasma membr ane, we found that significant amounts (5-14%) of all three subtypes could be identified in the biotinylated fractions of Jurkat and rat parotid cells . Our results suggest a role for IP,Rs in plasma membrane as well as intrac ellular membrane function.