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Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair.

Bouter A, Gounou C, Bérat R, Tan S, Gallois B, Granier T, d'Estaintot BL, Pöschl E, Brachvogel B, Brisson AR - Nat Commun (2011)

Bottom Line: Compared with wild-type mouse perivascular cells, AnxA5- cells exhibit a severe membrane repair defect.In contrast, an AnxA5 mutant that lacks the ability of forming 2D arrays is unable to promote membrane repair.We propose that AnxA5 participates in a previously unrecognized step of the membrane repair process: triggered by the local influx of Ca(2+), AnxA5 proteins bind to torn membrane edges and form a 2D array, which prevents wound expansion and promotes membrane resealing.

View Article: PubMed Central - PubMed

Affiliation: Molecular Imaging and NanoBioTechnology, IECB, UMR-5248 CBMN CNRS-University Bordeaux1-ENITAB, Talence F-33402, France.

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Model of cell membrane repair.(a) Intact cell membrane. The extracellular (Out) and intracellular (In) milieus differ by their high versus low Ca2+ concentrations, and the absence versus presence of AnxA5 (red rods) and PS (black spheres), respectively. (b) Local rupture of a cell membrane. Forces resulting from membrane tension tend to expand the tear laterally (black arrows). (c) The formation of an AnxA5 2D array at the torn membrane stops wound expansion. On membrane rupture, a microenvironment is formed in which the intracellular and extracellular milieus mix, providing optimal conditions for the formation of tight complexes between Ca2+, PS and AnxA5 (ref. 44). AnxA5 molecules bind to PS molecules exposed at ruptured membrane edges, form trimers and 2D arrays. These AnxA5 2D self-assemblies stabilize the membrane and stop expansion of the tear. (d) Top view of a membrane disruption with an AnxA5 2D array surrounding the tear. (e) Membrane resealing. Cytoplasmic vesicles are recruited at the ruptured membrane area and fuse by exocytosis with the plasma membrane, either directly as single vesicles or as a patch formed by homotypic fusion of intracellular vesicles19. The resulting increase in membrane surface and decrease in membrane tension lead to membrane resealing.
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f7: Model of cell membrane repair.(a) Intact cell membrane. The extracellular (Out) and intracellular (In) milieus differ by their high versus low Ca2+ concentrations, and the absence versus presence of AnxA5 (red rods) and PS (black spheres), respectively. (b) Local rupture of a cell membrane. Forces resulting from membrane tension tend to expand the tear laterally (black arrows). (c) The formation of an AnxA5 2D array at the torn membrane stops wound expansion. On membrane rupture, a microenvironment is formed in which the intracellular and extracellular milieus mix, providing optimal conditions for the formation of tight complexes between Ca2+, PS and AnxA5 (ref. 44). AnxA5 molecules bind to PS molecules exposed at ruptured membrane edges, form trimers and 2D arrays. These AnxA5 2D self-assemblies stabilize the membrane and stop expansion of the tear. (d) Top view of a membrane disruption with an AnxA5 2D array surrounding the tear. (e) Membrane resealing. Cytoplasmic vesicles are recruited at the ruptured membrane area and fuse by exocytosis with the plasma membrane, either directly as single vesicles or as a patch formed by homotypic fusion of intracellular vesicles19. The resulting increase in membrane surface and decrease in membrane tension lead to membrane resealing.

Mentions: According to current models, membrane resealing is an active process that requires extracellular Ca2+, intracellular vesicles and a step of Ca2+-dependent exocytosis1349. We propose that immediately after membrane rupture (Fig. 7a,b), AnxA5 participates in a previously unrecognized step of the repair process (Fig. 7c,d), which is followed by the membrane fusion events (Fig. 7e). Membrane ruptures create microenvironments in which extracellular and intracellular components mix; in particular, the high intracellular concentrations of PS and AnxA5 mix with the high extracellular concentration of Ca2+. Triggered by the local increase in Ca2+ concentration, AnxA5 binds to PS molecules exposed at the edges of torn membranes at which it self-assembles into 2D arrays. In vitro studies have indicated that AnxA5 2D arrays rigidify lipid monolayers and reduce the lateral diffusion of phospholipids4546. We propose that the formation of AnxA5 2D array at a ruptured membrane strengthens the membrane and prevents the expansion of the tear. By counteracting membrane tension due to cytoskeleton attachment, AnxA5 2D arrays promote membrane resealing in a way similar to that of other agents that lower membrane tension, similar to cytoskeleton depolymerizers7 or surfactants78.


Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair.

Bouter A, Gounou C, Bérat R, Tan S, Gallois B, Granier T, d'Estaintot BL, Pöschl E, Brachvogel B, Brisson AR - Nat Commun (2011)

Model of cell membrane repair.(a) Intact cell membrane. The extracellular (Out) and intracellular (In) milieus differ by their high versus low Ca2+ concentrations, and the absence versus presence of AnxA5 (red rods) and PS (black spheres), respectively. (b) Local rupture of a cell membrane. Forces resulting from membrane tension tend to expand the tear laterally (black arrows). (c) The formation of an AnxA5 2D array at the torn membrane stops wound expansion. On membrane rupture, a microenvironment is formed in which the intracellular and extracellular milieus mix, providing optimal conditions for the formation of tight complexes between Ca2+, PS and AnxA5 (ref. 44). AnxA5 molecules bind to PS molecules exposed at ruptured membrane edges, form trimers and 2D arrays. These AnxA5 2D self-assemblies stabilize the membrane and stop expansion of the tear. (d) Top view of a membrane disruption with an AnxA5 2D array surrounding the tear. (e) Membrane resealing. Cytoplasmic vesicles are recruited at the ruptured membrane area and fuse by exocytosis with the plasma membrane, either directly as single vesicles or as a patch formed by homotypic fusion of intracellular vesicles19. The resulting increase in membrane surface and decrease in membrane tension lead to membrane resealing.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3104517&req=5

f7: Model of cell membrane repair.(a) Intact cell membrane. The extracellular (Out) and intracellular (In) milieus differ by their high versus low Ca2+ concentrations, and the absence versus presence of AnxA5 (red rods) and PS (black spheres), respectively. (b) Local rupture of a cell membrane. Forces resulting from membrane tension tend to expand the tear laterally (black arrows). (c) The formation of an AnxA5 2D array at the torn membrane stops wound expansion. On membrane rupture, a microenvironment is formed in which the intracellular and extracellular milieus mix, providing optimal conditions for the formation of tight complexes between Ca2+, PS and AnxA5 (ref. 44). AnxA5 molecules bind to PS molecules exposed at ruptured membrane edges, form trimers and 2D arrays. These AnxA5 2D self-assemblies stabilize the membrane and stop expansion of the tear. (d) Top view of a membrane disruption with an AnxA5 2D array surrounding the tear. (e) Membrane resealing. Cytoplasmic vesicles are recruited at the ruptured membrane area and fuse by exocytosis with the plasma membrane, either directly as single vesicles or as a patch formed by homotypic fusion of intracellular vesicles19. The resulting increase in membrane surface and decrease in membrane tension lead to membrane resealing.
Mentions: According to current models, membrane resealing is an active process that requires extracellular Ca2+, intracellular vesicles and a step of Ca2+-dependent exocytosis1349. We propose that immediately after membrane rupture (Fig. 7a,b), AnxA5 participates in a previously unrecognized step of the repair process (Fig. 7c,d), which is followed by the membrane fusion events (Fig. 7e). Membrane ruptures create microenvironments in which extracellular and intracellular components mix; in particular, the high intracellular concentrations of PS and AnxA5 mix with the high extracellular concentration of Ca2+. Triggered by the local increase in Ca2+ concentration, AnxA5 binds to PS molecules exposed at the edges of torn membranes at which it self-assembles into 2D arrays. In vitro studies have indicated that AnxA5 2D arrays rigidify lipid monolayers and reduce the lateral diffusion of phospholipids4546. We propose that the formation of AnxA5 2D array at a ruptured membrane strengthens the membrane and prevents the expansion of the tear. By counteracting membrane tension due to cytoskeleton attachment, AnxA5 2D arrays promote membrane resealing in a way similar to that of other agents that lower membrane tension, similar to cytoskeleton depolymerizers7 or surfactants78.

Bottom Line: Compared with wild-type mouse perivascular cells, AnxA5- cells exhibit a severe membrane repair defect.In contrast, an AnxA5 mutant that lacks the ability of forming 2D arrays is unable to promote membrane repair.We propose that AnxA5 participates in a previously unrecognized step of the membrane repair process: triggered by the local influx of Ca(2+), AnxA5 proteins bind to torn membrane edges and form a 2D array, which prevents wound expansion and promotes membrane resealing.

View Article: PubMed Central - PubMed

Affiliation: Molecular Imaging and NanoBioTechnology, IECB, UMR-5248 CBMN CNRS-University Bordeaux1-ENITAB, Talence F-33402, France.

Show MeSH
Related in: MedlinePlus