Annexin A2-dependent actin bundling promotes secretory granule docking to the plasma membrane and exocytosis.
Bottom Line: Annexin A2, a calcium-, actin-, and lipid-binding protein involved in exocytosis, mediates the formation of lipid microdomains required for the structural and spatial organization of fusion sites at the plasma membrane.When an annexin A2 mutant with impaired actin filament-bundling activity was expressed, the formation of plasma membrane lipid microdomains and the number of exocytotic events were decreased and the fusion kinetics were slower, whereas the pharmacological activation of the intrinsic actin-bundling activity of endogenous annexin A2 had the opposite effects.Thus, annexin A2-induced actin bundling is apparently essential for generating active exocytotic sites.
Affiliation: Institut des Neurosciences Cellulaires et Intégratives, UPR3212 Centre National de la Recherche Scientifique, Université de Strasbourg, F-67084 Strasbourg, France.Show MeSH
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Mentions: The side-view of tilt transmission electron microscopy (TEM) series reconstructions of docked granules at different stages of fusion clearly showed that actin bundles linked secretory granules to the plasma membrane (PM) through specific membrane-associated structures (Fig. 3 A, V). These structures could correspond to the fine strands cross-linking granules to the plasma membrane previously revealed by quick-freeze, deep-etch electron microscopy (Nakata et al., 1990). These actin filaments were also observed when granules collapsed gradually to fuse with the plasma membrane. As recently described by Chiang et al. (2014), the size of the granules undergoing exocytosis seemed to decrease. It is interesting to note the positive curvature of the plasma membrane under docked granules that could be caused by forces exerted by the formation of actin bundles. Fig. 3 B shows that actin filaments connected secretory granules to the plasma membrane at anchor points localized in an area of 90–250 nm around the granule. This area corresponds to the 0.1-µm zone from the edge of granules where GM1 and AnxA2 beads were concentrated (Fig. 1 D; also see Fig. 4 B) and may constitute the dynamic platform in which protein and lipid diffusion is restricted (Saka et al., 2014).
Affiliation: Institut des Neurosciences Cellulaires et Intégratives, UPR3212 Centre National de la Recherche Scientifique, Université de Strasbourg, F-67084 Strasbourg, France.