Annexin A2–dependent actin bundling promotes secretory granule docking to the plasma membrane and exocytosis

Gabel, Marion; Delavoie, Franck; Demais, Valérie; Royer, Cathy; Bailly, Yannick; Vitale, Nicolas; Bader, Marie‐France; Chasserot‐Golaz, Sylvette

doi:10.1083/jcb.201412030

Cited by 76 publications

(69 citation statements)

References 56 publications

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“…With this dense actin network, granules near the plasma membrane, including NPY–mCherry-containing granules, were more associated with the F-actin network than those far from the plasma membrane (Fig. 4c), similar to a recent report with three-dimensional electron tomography24. We did not observe consistently actin rings surrounding NPY–EGFP-containing vesicles (Fig.…”

Section: Resultssupporting

confidence: 90%

“…4b), confirming a dense cortical actin network observed near, but not far from, the plasma membrane (see also Supplementary Fig. 9a,b for quantification)222324. With this dense actin network, granules near the plasma membrane, including NPY–mCherry-containing granules, were more associated with the F-actin network than those far from the plasma membrane (Fig.…”

Section: Resultssupporting

confidence: 68%

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Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane

et al. 2016

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Vesicle fusion is executed via formation of an Ω-shaped structure (Ω-profile), followed by closure (kiss-and-run) or merging of the Ω-profile into the plasma membrane (full fusion). Although Ω-profile closure limits release but recycles vesicles economically, Ω-profile merging facilitates release but couples to classical endocytosis for recycling. Despite its crucial role in determining exocytosis/endocytosis modes, how Ω-profile merging is mediated is poorly understood in endocrine cells and neurons containing small ∼30–300 nm vesicles. Here, using confocal and super-resolution STED imaging, force measurements, pharmacology and gene knockout, we show that dynamic assembly of filamentous actin, involving ATP hydrolysis, N-WASP and formin, mediates Ω-profile merging by providing sufficient plasma membrane tension to shrink the Ω-profile in neuroendocrine chromaffin cells containing ∼300 nm vesicles. Actin-directed compounds also induce Ω-profile accumulation at lamprey synaptic active zones, suggesting that actin may mediate Ω-profile merging at synapses. These results uncover molecular and biophysical mechanisms underlying Ω-profile merging.

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Section: Resultssupporting

confidence: 90%

Section: Resultssupporting

confidence: 68%

Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane

et al. 2016

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“…It is worth to mention that annexin‐A2 has also been identified among the spectrin interacting partners . Annexin‐A2 is a cytosolic protein that triggers the formation of actin bundles essential for the formation of active exocytotic sites in stimulated chromaffin cells . Whether spectrin is a hub involved in the recruitment to the exocytotic sites of the actin‐binding proteins (N‐WASP, annexin‐A2) required for building the actin architecture necessary for exocytosis remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, for a long time actin filament network was uniquely considered to be a physical barrier preventing the reserve pool of secretory vesicles to gain access to the plasma membrane. However, today this view has evolved toward a dynamic role of actin in which a complex process of actin filament remodeling is critically required for efficient exocytosis . Particularly, we have shown that neuronal Wiskott–Aldrich Syndrome protein (N‐WASP) is recruited at exocytic sites where its ability to promote actin filament assembly is necessary for exocytosis …”

Section: Introductionmentioning

confidence: 99%

αII‐spectrin controls calcium‐regulated exocytosis in neuroendocrine chromaffin cells through neuronal Wiskott–Aldrich Syndrome protein interaction

et al. 2019

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Besides a fundamental structural role at the plasma membrane, spectrin‐ and actin‐based skeletons have been proposed to participate in various processes including vesicular trafficking. Neuroendocrine cells release hormones and neuropeptides through calcium‐regulated exocytosis, a process that is coordinated by a fine remodeling of the actin cytoskeleton. We describe here that calcium‐regulated exocytosis is impaired in chromaffin and PC12 cells with reduced αII‐spectrin expression levels. Using yeast two‐hybrid screening, we show that neuronal Wiskott–Aldrich Syndrome protein (N‐WASP) is a partner of the αII‐spectrin SH3 domain and demonstrate that secretagogue‐evoked N‐WASP recruitment at cell periphery is blocked in the absence of αII‐spectrin. Additionally, experiments performed with ectopically expressed αII‐spectrin mutant unable to bind N‐WASP indicated that the interaction between SH3 domain and N‐WASP is pivotal for neuroendocrine secretion. Our results extend the list of spectrin interactors and strengthen the idea that αII‐spectrin is an important scaffold protein that gathers crucial actin‐related players of the exocytic machinery.

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“…Bovine chromaffin cells were washed with Locke's solution and processed for catecholamine release measurements by amperometry as described previously . Carbon‐fiber electrode of 5 μm diameter (ALA Scientific) was held at a potential of +650 mV compared with the reference electrode (Ag/AgCl) and approached closely to GFP expressing cells.…”

Section: Methodsmentioning

confidence: 99%

Phosphatidic acid metabolism regulates neuroendocrine secretion but is not under the direct control of lipins

et al. 2020

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Phosphatidic acid (PA) produced by phospholipase D1 has been shown to contribute to secretory vesicle exocytosis in a large number of cell models. Among various hypotheses, PA may contribute to recruit and/or activate at the exocytotic site a set of proteins from the molecular machinery dedicated to secretion, but also directly influence membrane curvature thereby favoring membrane rearrangements required for membrane fusion. The release of informative molecules by regulated exocytosis is a tightly controlled process. It is thus expected that PA produced to trigger membrane fusion should be rapidly metabolized and converted in a lipid that does not present similar characteristics. PA‐phosphatases of the lipin family are possible candidates as they convert PA into diacylglycerol. We show here that lipin 1 and lipin 2 are expressed in neuroendocrine cells where they are cytosolic, but also partially associated with the endoplasmic reticulum. Silencing of lipin 1 or 2 did not affect significantly either basal or evoked secretion from PC12 cells, suggesting that it is unlikely that conversion of PA into a secondary lipid by lipins might represent a regulatory step in exocytosis in neurosecretory cells. However, in agreement with a model in which PA‐metabolism could contribute to prevent entering into exocytosis of additional secretory vesicles, ectopic expression of lipin1B‐GFP in bovine chromaffin cells reduced the number of exocytotic events as revealed by carbon fiber amperometry recording. Furthermore, individual spike parameters reflecting fusion pore dynamics were also modified by lipin1B‐GFP, suggesting that a tight control of PA levels represents an important regulatory step of the number and kinetic of exocytotic events.

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Annexin A2–dependent actin bundling promotes secretory granule docking to the plasma membrane and exocytosis

Abstract: Annexin A2 and the actin cytoskeleton are essential partners in providing lipid platforms for granule recruitment and fusion during exocytosis.

Cited by 76 publications

References 56 publications

Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane

Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane

αII‐spectrin controls calcium‐regulated exocytosis in neuroendocrine chromaffin cells through neuronal Wiskott–Aldrich Syndrome protein interaction

Phosphatidic acid metabolism regulates neuroendocrine secretion but is not under the direct control of lipins

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