The Annexin II-p11 Complex Is Involved in Regulated Exocytosis in Bovine Pulmonary Artery Endothelial Cells

König, Julia; Prenen, Jean; Nilius, Bernd; Gerke, Volker

doi:10.1074/jbc.273.31.19679

Cited by 70 publications

(73 citation statements)

References 45 publications

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“…As previously shown (Powell and Glenney, 1987), Ca 2+ strongly enhanced cosedimentation of the annexin 2-p11 complex with control liposomes lacking phosphoinositides, although some complex was pelleted even in the presence of 1 mM EGTA. This is in line with previous experiments, showing a substantial binding of annexin 2-p11 to phosphoinositide-free liposomes at submicromolar Ca 2+ concentrations (König et al, 1998). When the liposomes contained PtdIns(4,5)P2, increased cosedimentation was observed, in particular in the absence of Ca 2+ (Fig.…”

Section: Resultssupporting

confidence: 81%

Annexin 2 is a phosphatidylinositol (4,5)-bisphosphate binding protein recruited to actin assembly sites at cellular membranes

Rescher¹,

Ruhe²,

Ludwig³

et al. 2004

Journal of Cell Science

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153

140

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Annexin 2 is a Ca2+-regulated membrane protein and an F-actin-binding protein enriched at actin assembly sites both, on the plasma membrane and on endosomal vesicles. Here, we identify annexin 2 as a phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2)-interacting protein, thereby explaining this specific membrane association. Using the pleckstrin-homology (PH) domain of phospholipase Cδ1 fused to yellow fluorescent protein as a marker for PtdIns(4,5)P2, we show that annexin 2 and its ligand p11 (S100A10) are targeted to sites of PtdIns(4,5)P2 enrichment where F-actin accumulates. At the plasma membrane, adhesion of pedestal-forming enteropathogenic Escherichia coli induces a recruitment of 1-phosphatidylinositol-4-phosphate 5-kinase (PtdIns4P 5-kinase) and an enrichment of PtdIns(4,5)P2 and annexin 2-p11 at sites of bacterial adhesion. Induction of PtdIns(4,5)P2-enriched ruffles and PtdIns(4,5)P2-positive, actin-coated vacuoles by Arf6-mediated activation of PtdIns4P 5-kinase also leads to a concomitant accumulation of the annexin 2-p11 complex and the PH domain. Binding studies with immobilized phosphoinositides and phosphoinositide-containing liposomes reveal that the purified annexin 2-p11 complex directly and specifically binds to PtdIns(4,5)P2 with an affinity comparable to that of the PH domain of phospholipase Cδ1. Experiments using individual subunits identify annexin 2 as the PtdIns(4,5)P2-binding entity. Thus, the direct interaction of annexin 2 with PtdIns(4,5)P2 is a means of specifically recruiting the annexin 2-p11 complex to sites of membrane-associated actin assembly.

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Section: Resultssupporting

confidence: 81%

Annexin 2 is a phosphatidylinositol (4,5)-bisphosphate binding protein recruited to actin assembly sites at cellular membranes

Rescher¹,

Ruhe²,

Ludwig³

et al. 2004

Journal of Cell Science

Self Cite

153

140

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“…Thus, Anx2 is associated with the regulation of DNA synthesis, and probably also with the cell cycle (Chiang et al, 1993) and cellular proliferation (Kumble et al, 1992b). Other functions include regulation of membrane trafficking such as exocytosis (Liu et al, 1996;Konig et al, 1998) and actin filament bundling (Jones et al, 1992), immunosuppression in RCC (Aarli et al, 1997) and insulin-induced signal transduction (Biener et al, 1996). However, few studies have focused on the role of Anx2 in the pathological conditions induced by ROS.…”

Section: Discussionmentioning

confidence: 99%

Redox regulation of annexin 2 and its implications for oxidative stress-induced renal carcinogenesis and metastasis

et al. 2004

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“…1 WPB exocytosis is triggered by increases in intracellular free Ca 2ϩ or cAMP concentrations, and involves a number of molecular components, including the Nethylmaleimide-sensitive factor, VAMP3, SNAP23, syntaxin 4, RalA, the annexin A2/S100A10 complex, and phospholipase D. [2][3][4][5][6][7] In addition, Rab proteins also regulate WPB exocytosis. A subset of Rab proteins, including Rab3A-3D, Rab27A/B, and Rab37, is associated with SGs in different cell types where they regulate SG biogenesis, trafficking, and exocytosis.…”

Section: Introductionmentioning

confidence: 99%

The interplay between the Rab27A effectors Slp4-a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis

Bierings

Hellen

Kiskin

et al. 2012

Blood

166

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Weibel-Palade body (WPB) exocytosis underlies hormone-evoked VWF secretion from endothelial cells (ECs). We identify new endogenous components of the WPB: Rab3B, Rab3D, and the Rab27A/ Rab3 effector Slp4-a (granuphilin), and determine their role in WPB exocytosis. We show that Rab3B, Rab3D, and Rab27A contribute to Slp4-a localization to WPBs. siRNA knockdown of Slp4-a, MyRIP, Rab3B, Rab3D, Rab27A, or Rab3B/ Rab27A, or overexpression of EGFPSlp4-a or EGFP-MyRIP showed that Slp4-a is a positive and MyRIP a negative regulator of WPB exocytosis and that Rab27A alone mediates these effects. We found that ECs maintain a constant amount of cellular Rab27A irrespective of the WPB pool size and that Rab27A (and Rab3s) cycle between WPBs and a cytosolic pool. The dynamic redistribution of Rab proteins markedly decreased the Rab27A concentration on individual WPBs with increasing WPB number per cell. Despite this, the probability of WPB release was independent of WPB pool size showing that WPB exocytosis is not determined simply by the absolute amount of Rab27A and its effectors on WPBs. Instead, we propose that the probability of release is determined by the fractional occupancy of WPB-Rab27A by Slp4-a and MyRIP, with the balance favoring exocytosis. (Blood. 2012;120(13):2757-2767) IntroductionHormone-evoked VWF secretion from endothelial cells (ECs) is mediated by exocytosis of specialized secretory granules (SGs) called Weibel-Palade bodies (WPBs). 1 WPB exocytosis is triggered by increases in intracellular free Ca 2ϩ or cAMP concentrations, and involves a number of molecular components, including the Nethylmaleimide-sensitive factor, VAMP3, SNAP23, syntaxin 4, RalA, the annexin A2/S100A10 complex, and phospholipase D. [2][3][4][5][6][7] In addition, Rab proteins also regulate WPB exocytosis. A subset of Rab proteins, including Rab3A-3D, Rab27A/B, and Rab37, is associated with SGs in different cell types where they regulate SG biogenesis, trafficking, and exocytosis. 8 Secretory cells often express a mixture of these "secretory" Rabs, which may have overlapping or distinct functions. Human ECs are reported to express mRNA for Rab3A, Rab3D, and Rab37,3,9,10 Rab3B protein, 11 and Rab27A mRNA and protein. 12,13 To date, Rab27A is the only endogenous EC Rab protein that has been detected on WPBs. Through its effector MyRIP and Myosin Va, Rab27A is proposed to negatively regulate WPB exocytosis. 13,14 Rab27A can interact with different effector molecules, and many secretory cells express a mixture of these effectors. 8 In these cases, SG exocytosis probably depends on the balance of Rab27A interactions with the complement of Rab effectors in the cell.In addition to MyRIP, ECs contain mRNA for the Rab27A effector Slp4-a (granuphilin). 13 Slp4-a links SGs to the plasma membrane (PM) through SG-associated Rab proteins (principally Rab27A), PM-associated syntaxins (1a, 2, or 3) and soluble Munc18 isoforms. [15][16][17][18][19] Syntaxins exist in open and closed conformations that determine their participation in SNARE complex f...

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The Annexin II-p11 Complex Is Involved in Regulated Exocytosis in Bovine Pulmonary Artery Endothelial Cells

Cited by 70 publications

References 45 publications

Annexin 2 is a phosphatidylinositol (4,5)-bisphosphate binding protein recruited to actin assembly sites at cellular membranes

Annexin 2 is a phosphatidylinositol (4,5)-bisphosphate binding protein recruited to actin assembly sites at cellular membranes

Redox regulation of annexin 2 and its implications for oxidative stress-induced renal carcinogenesis and metastasis

The interplay between the Rab27A effectors Slp4-a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis

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