Annexin A2 Egress during Calcium-Regulated Exocytosis in Neuroendocrine Cells.

Marion Gabel,Marie-France Bader,Sylvette Chasserot-Golaz,Nicolas Vitale,Valérie Calco,Stéphane Gasman,Tamou Thahouly,Cathy Royer

doi:10.3390/cells9092059

Marion Gabel, Marie-France Bader + Show 6 more

Open Access

https://doi.org/10.3390/cells9092059

Copy DOI

Abstract

Annexin A2 (AnxA2) is a calcium- and lipid-binding protein involved in neuroendocrine secretion where it participates in the formation and/or stabilization of lipid micro-domains required for structural and spatial organization of the exocytotic machinery. We have recently described that phosphorylation of AnxA2 on Tyr23 is critical for exocytosis. Considering that Tyr23 phosphorylation is known to promote AnxA2 externalization to the outer face of the plasma membrane in different cell types, we examined whether this phenomenon occurred in neurosecretory chromaffin cells. Using immunolabeling and biochemical approaches, we observed that nicotine stimulation triggered the egress of AnxA2 to the external leaflets of the plasma membrane in the vicinity of exocytotic sites. AnxA2 was found co-localized with tissue plasminogen activator, previously described on the surface of chromaffin cells following secretory granule release. We propose that AnxA2 might be a cell surface tissue plasminogen activator receptor for chromaffin cells, thus playing a role in autocrine or paracrine regulation of exocytosis.

Highlights

Molecules such as neurotransmitters and hormones are secreted by calcium-regulated exocytosis [1,2]
We have found that Annexin A2 (AnxA2) needs to be phosphorylated on Tyr23 to stabilize the lipid platform determining the exocytotic site, and dephosphorylated to bundle actin filaments for stably anchoring granules, implying that the phosphorylation cycle of AnxA2 on Tyr23 is critical for neuroendocrine secretion [6]
Having recently shown that the AnxA2 is phosphorylated on Tyr23 during exocytosis [6], we examined whether Tyr23 phosphorylation of AnxA2 could lead to its externalization in chromaffin cells

Summary

Introduction

Molecules such as neurotransmitters and hormones are secreted by calcium-regulated exocytosis [1,2]. Exocytosis implies the recruitment and subsequent fusion of secretory granules at specific sites of the plasma membrane. Is a promoter of these sites of exocytosis in cells activated for secretion. Electron tomography has revealed that actin filaments bundled by AnxA2 contribute to the formation of lipid micro-domains at the plasma membrane required for the spatial and functional organization of the exocytotic machinery [3,4,5]. We have found that AnxA2 needs to be phosphorylated on Tyr to stabilize the lipid platform determining the exocytotic site, and dephosphorylated to bundle actin filaments for stably anchoring granules, implying that the phosphorylation cycle of AnxA2 on Tyr is critical for neuroendocrine secretion [6]

Methods

Results

Conclusion