Identification of a novel protein complex containing annexin A4, rabphilin and synaptotagmin

Willshaw, Angela; Grant, Karen M.; Yan, Jun; Rockliffe, Nichola; Ambavarapu, Sailaja; Burdyga, Galina; Varró, Andrea; Fukuoka, Shin-Ichi; Gawler, Debra J.

doi:10.1016/s0014-5793(03)01513-8

Cited by 18 publications

(15 citation statements)

References 43 publications

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“…We observed a decreased content of calponin-2, a protein that is involved in cell motility and cytokinesis [63] and a decreased abundance of annexin A4, which plays a role in exocytosis [64]. These two proteins are involved in exchange mechanisms with the environment of the cell; the results reported here thus suggest that cells chronically-exposed to TiO 2 -NPs reduce their communication with the extracellular compartment due to the intracellular stress [65].…”

Section: Accepted Manuscriptmentioning

confidence: 51%

Molecular responses of alveolar epithelial A549 cells to chronic exposure to titanium dioxide nanoparticles: A proteomic view

Armand

Biola-Clier

Bobyk

et al. 2016

Journal of Proteomics

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Our results make possible the identification of new mechanisms that explain TiO2-NP toxicity upon long-term, in vitro exposure of A549 cells. It is the first article describing -omics results obtained with this experimental strategy. We show that this long-term exposure modifies the cellular content of proteins involved in functions including mitochondrial activity, intra- and extracellular trafficking, proteasome activity, glucose metabolism, and gene expression. Moreover we observe modification of content of proteins that activate the p53 pathway, which suggest the induction of a DNA damage response. Technically, our results show that exposure of A549 cells to a high concentration of TiO2-NPs leads to the identification of modulations of the same functional categories than exposure to low, more realistic concentrations. Still the intensity differs between these two exposure scenarios. We also show that chronic exposure to TiO2-NPs induces the modulation of cellular functions that have already been reported in the literature as being impacted in acute exposure scenarios. This proves that the exposure protocol in in vitro experiments related to nanoparticle toxicology might be cautiously chosen since inappropriate scenario may lead to inappropriate and/or incomplete conclusions.

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Section: Accepted Manuscriptmentioning

confidence: 51%

Molecular responses of alveolar epithelial A549 cells to chronic exposure to titanium dioxide nanoparticles: A proteomic view

Armand

Biola-Clier

Bobyk

et al. 2016

Journal of Proteomics

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“…␣-actinin, ␤-adducin, GTP cyclohydrolase I, Rabaptin5, and annexin A4) (43)(44)(45)(46)(47)(48) have no relation to the function of neuronal SNAREs or SNARE-related proteins, and a physical association between rabphilin and SNAREs had never been elucidated even in vitro. In the present study we obtained for the first time biochemical evidence that the C2B domain of rabphilin is necessary and sufficient for direct Ca 2ϩ -independent interaction with SNAP-25 but not with syntaxin IA or VAMP-2 (Figs.…”

Section: Discussionmentioning

confidence: 99%

The C2B Domain of Rabphilin Directly Interacts with SNAP-25 and Regulates the Docking Step of Dense Core Vesicle Exocytosis in PC12 Cells

Tsuboi¹,

Fukuda

2005

Journal of Biological Chemistry

141

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Rabphilin is a membrane trafficking protein on secretory vesicles that consists of an N-terminalRabphilin was originally identified as a specific GTP-Rab3A-binding protein on secretory granules (1, 2) that is involved in the control of regulated secretion, including neurotransmitter release and hormone secretion (3-6). Recent evidence, however, has indicated that rabphilin functions independently of Rab3A. First, rabphilin knock-out animals and Rab3 knock-out animals display distinct phenotypes in terms of neurotransmitter release (7,8). Second, rabphilin promotes dense core vesicle exocytosis by endocrine cells independently of Rab3A (9, 10). Third, we very recently found that an N-terminal Rab-binding domain (RBD) 3 of rabphilin also functions as an effector domain for Rab27A in PC12 cells (11)(12)(13)(14). Although the Rab binding properties of rabphilin have been well documented (1,(11)(12)(13)(14)(15)(16), the function of the C-terminal tandem C2 domains of rabphilin, upon ligand binding during regulated secretion remains largely unknown. Biochemical analysis has indicated that the C2 domains of rabphilin interact with phospholipids in a Ca 2ϩ -dependent manner (17-19), but how the Ca 2ϩ /phospholipid binding to the C2 domains of rabphilin triggers regulated secretion also remains unknown.The functional relationship between Rab27A⅐effector complex and SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, fundamental fusion machinery of vesicle exocytosis (20), have recently been reported. Slp4-a/granuphilin-a, another Rab27A effector that functions in certain endocrine cells (21-23) and parotid acinar cells (24), was reported to directly interact with syntaxin IA and/or Munc18-1 (23, 25, 26). In addition, the results of a genetic analysis of Caenorhabditis elegans rabphilin and SNARE (syntaxin, SNAP-25, or VAMP/synaptobrevin) double mutants have suggested that rabphilin modulates SNARE function (8). Thus, it is highly possible that rabphilin physically associates with SNARE proteins itself and/or SNARE-associated proteins but that possibility has never been investigated. In this study we systematically investigated the interaction between rabphilin and SNAREs and SNARE-associated proteins by coimmunoprecipitation assays and found that the C2B domain of rabphilin directly interacts with isolated SNAP-25, a target SNARE localized on the plasma membrane. Because there has never been a detailed description of the function of the C2B domain of rabphilin in the recruitment, docking, priming, and fusion of secretory vesicles in live cells, we also investigated the function of the C2B domain of rabphilin on the motion of a single dense core vesicle during exocytosis in PC12 cells by total internal reflection fluorescence microscopy (TIRF, also called evanescent wave or evanescence microscopy) (27) using vesicletargeted fluorescent proteins (28 -31). Expression of the rabphilin-⌬C2B mutant lacking SNAP-25 binding activity inhibited vesicle docking and markedly decreased the number...

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“…1). Anxa4 promotes vesicle aggregation in vitro, plays an important role in synaptic exocytosis and membrane repair [13,14]; it also regulates Ca 2+ -activated Cl − conductance, alters the physical properties of membranes to regulate passive membrane permeability [15][16][17], and induces calcium signaling, anticoagulation, and resistance to apoptosis [18]. Anxa4 has been reported to be associated with the progression, invasion, migration, adhesion, and drug resistance of a variety of cancers [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Annexin A4 and cancer

Wei

Guo

Liu

et al. 2015

Clinica Chimica Acta

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Identification of a novel protein complex containing annexin A4, rabphilin and synaptotagmin

Cited by 18 publications

References 43 publications

Molecular responses of alveolar epithelial A549 cells to chronic exposure to titanium dioxide nanoparticles: A proteomic view

Molecular responses of alveolar epithelial A549 cells to chronic exposure to titanium dioxide nanoparticles: A proteomic view

The C2B Domain of Rabphilin Directly Interacts with SNAP-25 and Regulates the Docking Step of Dense Core Vesicle Exocytosis in PC12 Cells

Annexin A4 and cancer

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