Annexin 2 "secretion" accompanying exocytosis of chromaffin cells: possible mechanisms of annexin release.
Annexin 2 is a Ca(2+)-dependent phospholipid-binding protein that is involved in secretion. Despite the fact that this protein does not have signals for its secretion, many reports have shown its presence in the extracellular milieu. Here we demonstrate that, upon stimulation of exocytosis in chromaffin cells, a fraction of annexin 2 is secreted into the culture medium. This release of annexin 2 is specific, correlated with catecholamine secretion, and independent of cell death. To explain the liberation of cytosolic annexin 2 into the medium, we propose and bring evidence for a mechanism of multiporic membrane disruption during membrane fusion. Prior, in cross-linking experiments, annexin 2 forms aggregates of high molecular weight, revealing its capacity to form networks. Second, immunoelectron microscopy studies of fused chromaffin granules revealed the presence of annexin 2 and membrane proteins inside the fused vesicles, as would be predicted by the multiporic hypotheses. These data suggest that annexin 2 "secretion" in chromaffin cells is the consequence of membrane disruption during exocytosis. The role of annexin 2 in exocytosis is also discussed.
Faure
Ariane-Valérie
AV
INSERM U332, Signalisation, Inflammation et Transformation Cellulaire, 22 rue Méchain, 75014 Paris, France.
Migné
Carole
C
Devilliers
Ginnette
G
Ayala-Sanmartin
Jesus
J
D000818:Animals; D017306:Annexin A2 / Q000032:analysis / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005089:Exocytosis; D008561:Membrane Fusion; D008954:Models, Biological; D009538:Nicotine / Q000494:pharmacology; D022142:Secretory Vesicles / Q000737:chemistry / Q000648:ultrastructure
D017306:Annexin A2; D009538:Nicotine