Endocrine Abstracts

Annexin 1 (ANXA1) belongs to a well-conserved superfamily of structurally-related Ca²⁺ and phospholipid-binding proteins. We first described its induction and role as a mediator of glucocorticoid (GC) actions within the host defence and neuroendocrine systems. In addition we provided evidence that an extracellular pool of ANXA1 is responsible for many of the regulatory actions of the protein, particularly in the pituitary gland where ANXA1 exported from folliculostellate (FS) cells appears to act as a paracrine agent, exerting important regulatory effects on the corticotrophs and other endocrine cells. The extracellular pool of ANXA1 is regulated by GCs which, in addition to inducing de novo ANXA1 synthesis via genomic mechanisms, cause translocation of a serine phosphorylated species of the protein (27-Ser-P ANXA1) to the outer cell membrane, apparently via a novel non-genomic mechanism. To explore further the mechanisms effecting the transfer of ANXA1 across the membrane, we have transfected TtT/GF cells (murine FS line) with wild type or mutated ANXA1 green fluorescence tagged (GFP) constructs. Exposure of TtT/GF cells to dexamethasone (1 micromolar, 30 minutes), caused prompt translocation of 27-Ser-P ANXA1 to the cell surface. By contrast, cells overexpressing a mutant form of ANXA1 in which the serine-27 was replaced with alanine were unresponsive to these stimuli. These results suggest that 27-serine phosphoryation is essential for the translocation of ANXA1 across the cell membrane and that GPF-tagged-ANXA1 will provide a valuable tool with which to explore the mechanisms of translocation further.

This work was supported by the Wellcome Trust.