Characterisation of the sarcoidosis-associated variant of annexin A11

Recent studies on the genetic background of sarcoidosis have resulted in the discovery of a strongly associated single nucleotide polymorphism (SNP) that switches a highly conserved arginine to a cysteine at position 230 in annexin A11. The effect of the R230C SNP on the cellular distribution and Ca(2+)-sensitivity of annexin A11 was investigated through over-expression of GFP tagged annexin A11 in A431 cells. Cells were stimulated with calcium mobilizing agonists and changes in the cellular localisation of GFP tagged annexin A11 were recorded. Neither variant of annexin 11, nor any truncation mutants, exhibited any response to EGF. In addition, there was no relocalisation of the GFP tagged C-terminal annexin A11 variants in response to ionomycin. However, both the wild type and sarcoidosis associated variants of annexin A11-GFP relocalised to the plasma membrane and then the nuclear envelope in response to ionomycin. These observations show that the sensitivity of annexin A11 to a robust, sustained rise in intracellular calcium, is not significantly affected by the sarcoidosis associated SNP. This does not rule out functional affects in the extracellular milieu, in cytokinesis, nuclear envelope breakdown or in response to other intracellular signals.