Novel Organization and Properties of Annexin 2-Membrane Complexes

Lambert, Olivier; Cavusoglu, Nükhet; Gallay, Jacques; Vincent, Michel; Rigaud, Jean‐Louis; Henry, Jean‐Pierre; Ayala-Sanmartín, Jesús

doi:10.1074/jbc.m313657200

Cited by 41 publications

(47 citation statements)

References 65 publications

(104 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At mild acidic pH, AIIt undergoes conformational changes similar to those induced by Ca 2 þ . Thus, ANX II appears to have access to the hydrophobic part of the cellular membranes at both acidic pH in the absence of Ca 2 þ and at neutral pH in the presence of Ca 2 þ (Lambert et al, 2004). This may explain our findings of a significant increase in the crosslinking of gastrins to ANX II (B32-36 kDa) at slightly acidic pH (Figure 3b).…”

Section: Identification Of Proteins In Band C By Seldi-tof-ms and Malmentioning

confidence: 59%

Annexin II binds progastrin and gastrin-like peptides, and mediates growth factor effects of autocrine and exogenous gastrins on colon cancer and intestinal epithelial cells

Singh

Clark³

et al. 2006

Oncogene

View full text Add to dashboard Cite

We and others have reported the presence of novel progastrin (PG)/gastrin receptors on normal and cancerous intestinal cells. We had earlier reported the presence of 33-36 kDa gastrin-binding proteins on cellular membranes of colon cancer cells. The goal of the current study was to identify the protein(s) in the 33-36 kDa band, and analyse its functional significance. A carbodiimide crosslinker was used for crosslinking radio-labeled gastrins to membrane proteins from gastrin/PG responsive cell lines. Native membrane proteins, crosslinked to the ligand, were solubulized and enriched by >1000-fold, and analysed by surface-enhanced laser desorption/ ionization-time of flight-mass spectrometry. The peptide masses were researched against the NCBInr database using the ProFound search engine. Annexin II (ANX II) was identified, and confirmed by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. As HCT-116 cells express autocrine PG, the in situ association of PG with ANX II was demonstrated in pulldown assays. Direct binding of PG with ANX II was confirmed in an in vitro binding assay. In order to confirm a functional importance of these observations, sense and anti-sense (AS) ANX II RNA-expressing clones of intestinal epithelial (IEC-18) and human colon cancer (HCT-116) cell lines were generated. AS clones demonstrated a significant loss in the growth response to exogenous (IEC-18) and autocrine (HCT-116) PG. We have thus discovered that membrane-associated ANX II binds PG/gastrins, and partially mediates growth factor effects of the peptides.

show abstract

Section: Identification Of Proteins In Band C By Seldi-tof-ms and Malmentioning

confidence: 59%

Annexin II binds progastrin and gastrin-like peptides, and mediates growth factor effects of autocrine and exogenous gastrins on colon cancer and intestinal epithelial cells

Singh

Clark³

et al. 2006

Oncogene

View full text Add to dashboard Cite

show abstract

“…This could allow them to organize the interface between the cytoplasm (or cytoskeleton) and the cytoplasmic face of cellular membranes. In fact, cryoelectron and atomic force microscopy of annexins bound to model membranes have provided compelling images of the proteins forming two-dimensional lattices or certain domains on the surface of membranes (Janshoff et al, 2001;Lambert et al, 1997;Reviakine et al, 2000;Lambert et al, 2004). Although the coating of target membranes to establish and/or regulate lateral membrane domains is likely to be a key element of annexin function, a few questions remain.…”

Section: Annexins As Membrane Scaffold Proteinsmentioning

confidence: 99%

Annexins – unique membrane binding proteins with diverse functions

Rescher

Gerke

2004

Journal of Cell Science

538

435

View full text Add to dashboard Cite

IntroductionThe annexins are a family of Ca 2+ /lipid-binding proteins that differ from most other Ca 2+ -binding proteins in their Ca 2+ -binding sites. These have a unique architecture that allows them to dock onto membranes in a peripheral and reversible manner. The conserved Ca 2+ -and membrane-binding module is the annexin core domain, which consists of four so-called annexin repeats, each of which is 70 residues in length. It is highly α-helical and forms a compact, slightly curved disc that has a convex surface harboring the Ca 2+ -and membranebinding sites and a concave side that points away from the membrane and is thereby available for other types of interaction/regulation (Fig. 1). The N-terminal region precedes the core domain and is diverse in sequence and length. It mediates regulatory interactions with protein ligands and regulates the annexin-membrane association (reviewed by Gerke and Moss, 2002;Raynal and Pollard, 1994). Although the N-terminal domain has long been considered a separately folded entity, recent crystal structures reveal that, at least in annexin A1, part of it can integrate into the folded core. Ca 2+ (and probably membrane) binding can then trigger exposure of the N-terminal region, making it available for additional interactions/activities ( Fig. 1) (Rosengarth and Luecke, 2003). The activity of the exposed N-terminal region could thus be tightly controlled through Ca 2+ /membrane binding.The annexin family comprises >500 different gene products expressed in most phyla and species (reviewed by Morgan and Fernandez, 1997). In vertebrates, 12 annexin subfamilies (A1-A11 and A13), which have different splice variants, have been identified. These have different N-terminal domains and differently positioned Ca 2+ /membrane-binding sites within the core domain. Analyses of the biochemical properties and subcellular localizations of annexins, and later studies of the effects of anti-annexin antibodies and annexin mutants, mainly in permeabilized cell systems, have allowed several potential physiological functions to be assigned to different annexins. Most of these take into account their regulated binding to membranes and a scaffold role at certain membrane domains is a common theme.Proposed to act as membrane-membrane or membranecytoskeleton linkers, annexins have been implicated in Ca 2+ -regulated exocytotic events, certain aspects of endocytosis and stabilization of specific domains of organelle membranes and the plasma membrane. However, other potential functions have been put forward -for example, those taking into account the RNA-binding capacity of some annexins (Filipenko et al., 2004;Vedeler and Hollas, 2000), their regulated nuclear localization (Eberhard et al., 2001;Mizutani et al., 1992;Tomas and Moss, 2003) or specific nucleotide-binding activities (Banderowicz-Pikula et al., 2001; Caohuy et al., 1996). Because some annexins occur extracellularly, they might also function outside the cell, although their (direct or indirect) secretion is not well understood. Detailed ...

show abstract

“…AnxA2 is a soluble protein predominantly distributed in the cytosol of the cells at resting Ca 2ϩ levels and translocated to cellular membranes under elevated concentrations of intracellular Ca 2ϩ (3). In vitro studies using artificial membranes have shown that AnxA2 preferentially binds to the acidic phospholipids, which are enriched in the cytoplasmic leaflet of cellular membranes (4).…”

Section: Anxa2mentioning

confidence: 99%

Lipid Raft Endocytosis and Exosomal Transport Facilitate Extracellular Trafficking of Annexin A2

Valapala

Vishwanatha

2011

Journal of Biological Chemistry

170

150

View full text Add to dashboard Cite

Annexin A2 (AnxA2), a Ca 2؉ -dependent phospholipid-binding protein, is known to associate with the plasma membrane and the endosomal system. Within the plasma membrane, AnxA2 associates in a Ca 2؉ dependent manner with cholesterolrich lipid raft microdomains. Here, we show that the association of AnxA2 with the lipid rafts is influenced not only by intracellular levels of Ca 2؉ but also by N-terminal phosphorylation at tyrosine 23. Binding of AnxA2 to the lipid rafts is followed by the transport along the endocytic pathway to be associated with the intralumenal vesicles of the multivesicular endosomes. AnxA2-containing multivesicular endosomes fuse directly with the plasma membrane resulting in the release of the intralumenal vesicles into the extracellular environment, which facilitates the exogenous transfer of AnxA2 from one cell to another. Treatment with Ca 2؉ ionophore triggers the association of AnxA2 with the specialized microdomains in the exosomal membrane that possess raft-like characteristics. Phosphorylation at Tyr-23 is also important for the localization of AnxA2 to the exosomal membranes. These results suggest that AnxA2 is trafficked from the plasma membrane rafts and is selectively incorporated into the lumenal membranes of the endosomes to escape the endosomal degradation pathway. The Ca 2؉ -dependent exosomal transport constitutes a novel pathway of extracellular transport of AnxA2.

show abstract

Novel Organization and Properties of Annexin 2-Membrane Complexes

Cited by 41 publications

References 65 publications

Annexin II binds progastrin and gastrin-like peptides, and mediates growth factor effects of autocrine and exogenous gastrins on colon cancer and intestinal epithelial cells

Annexin II binds progastrin and gastrin-like peptides, and mediates growth factor effects of autocrine and exogenous gastrins on colon cancer and intestinal epithelial cells

Annexins – unique membrane binding proteins with diverse functions

Lipid Raft Endocytosis and Exosomal Transport Facilitate Extracellular Trafficking of Annexin A2

Contact Info

Product

Resources

About