Identification of an AHNAK Binding Motif Specific for the Annexin2/S100A10 Tetramer

Seranno, Sandrine De; Benaud, Christelle; Assard, Nicole; Khediri, Sami; Gerke, Volker; Baudier, Jacques; Delphin, Christian

doi:10.1074/jbc.m606545200

Cited by 37 publications

(51 citation statements)

References 49 publications

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“…This correlates with the fact that A2 docks with these specific sites when VE-cad-mediated adherens junctions reach maturity. Although the mechanism underlying the A2 targeting to membrane as cell confluence is established remains to be elucidated, it probably requires the formation of the heterotetramer (A2) 2 (p11) 2 (14). Indeed, immunofluorescent labeling of p11 and A2 perfectly overlapped with that of VE-cad at cell-cell junctions (data not shown).…”

Section: Discussionmentioning

confidence: 94%

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Contribution of Annexin 2 to the Architecture of Mature Endothelial Adherens Junctions

Heyraud

Jaquinod

Durmort

et al. 2008

Molecular and Cellular Biology

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The vascular endothelial cadherin (VE-cad)-based complex is involved in the maintenance of vascular endothelium integrity. Using immunoprecipitation experiments, we have demonstrated that, in confluent human umbilical vein endothelial cells, the VE-cad-based complex interacts with annexin 2 and that annexin 2 translocates from the cytoplasm to the cell-cell contact sites as cell confluence is established. Annexin 2, located in cholesterol rafts, binds to both the actin cytoskeleton and the VE-cad-based complex so the complex is docked to cholesterol rafts. These multiple connections prevent the lateral diffusion of the VE-cad-based complex, thus strengthening adherens junctions in the ultimate steps of maturation. Moreover, we observed that the down-regulation of annexin 2 by small interfering RNA induces a delocalization of VE-cad from adherens junctions and consequently a destabilization of these junctions. Furthermore, our data indicate that the decoupling of the annexin 2/p11 complex from the VE-cad-based junction, triggered by vascular endothelial growth factor treatment, facilitates the switch from a quiescent to an immature state.Vascular endothelium consists of a monolayer of endothelial cells which lines the whole vascular tree. It forms an active boundary between the bloodstream and the underlying tissues, thus controlling the movement of circulating white cells between blood and inflamed tissues. The endothelium is also at the origin of the extension of preexisting vasculature through formation of neo-vessels, a process named angiogenesis (43). Adherens and tight junctions which hold together endothelial cells modulate leukocyte traffic and angiogenesis. Without diminishing the importance of tight junctions, adherens junctions are particularly crucial in controlling the formation and maintenance of interendothelial adhesion.Endothelial cells express a cell-specific cadherin designated vascular endothelial cadherin (VE-cad) which constitutes the main component of interendothelial adherens junctions (4,12,30). This transmembrane adhesive protein plays a crucial role in the maintenance of endothelium integrity and in the modulation of its permeability (3,20). As for other members of the cadherin receptor family, VE-cad links endothelial cells together by homophilic interactions mediated by its extracellular part and associates intracellularly with ␤-or ␥-catenin in a mutually exclusive fashion and with p120. Despite their sequence similarities, ␤/␥-catenins and p120 bind to distinct sites on the cytoplasmic tail of VE-cad. While ␤-catenin or ␥-catenin links to the distal part of the VE-cad cytoplasmic tail, p120 interacts with the membrane-proximal domain. These three catenins also exhibit different biological cellular roles. Whereas p120 stabilizes VE-cad at the plasma membrane (46, 47), ␤/␥-catenins interact with ␣-catenin. Subsequently in this article, the complex formed by VE-cad and p120 ␣-, ␤-, and ␥-catenins will be designated as the "VE-cad-based complex" or "VE-cad complex."Until recently, it wa...

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Section: Discussionmentioning

confidence: 94%

“…A2 interacts, via its N-terminal domain, with p11 (also called S100A10) to form a heterotetramer in which a central p11 dimer connects two A2 monomers (14,26,32). Moreover, A2 exhibits an F-actin binding site localized within the last 9 amino acid residues of its C terminus (17).…”

mentioning

confidence: 99%

Contribution of Annexin 2 to the Architecture of Mature Endothelial Adherens Junctions

Heyraud

Jaquinod

Durmort

et al. 2008

Molecular and Cellular Biology

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“…It has previously been established that the affinity of AHNAK for S100A10 is much greater when AnxA2 is bound (De Seranno et al, 2006). Indeed, the crystal structure reveals direct interactions between the AnxA2 and AHNAK peptides.…”

mentioning

confidence: 88%

“…AHNAK, a large 629 kDa protein, has been implicated in membrane repair, and the annexin A2-S100A10 heterotetramer [(p11) 2 (AnxA2) 2 ] has high affinity for several regions of the long (1002-amino-acid) C-terminal domain of AHNAK (Shtivelman & Bishop, 1993;Benaud et al, 2004;Huang et al, 2007;Lennon et al, 2003;De Seranno et al, 2006;Rezvanpour et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…The binding interaction of AHNAK with (p11) 2 (AnxA2) 2 has been studied more extensively, and a minimal binding motif has been mapped to a 20-amino-acid peptide corresponding to residues 5654-5673 of the AHNAK C-terminal domain (De Seranno et al, 2006;Rezvanpour et al, 2011). Various biophysical studies have also shown that the AnxA2 N-terminal domain is necessary for high-affinity binding of S100A10 to AHNAK.…”

Section: Introductionmentioning

confidence: 99%

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Structure of a C-terminal AHNAK peptide in a 1:2:2 complex with S100A10 and an acetylated N-terminal peptide of annexin A2

Ozorowski

Milton

Luecke

2012

Acta Crystallogr D Biol Crystallogr

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AHNAK, a large 629 kDa protein, has been implicated in membrane repair, and the annexin A2–S100A10 heterotetramer [(p11)2(AnxA2)2)] has high affinity for several regions of its 1002‐amino‐acid C‐terminal domain. (p11)2(AnxA2)2 is often localized near the plasma membrane, and this C2‐symmetric platform is proposed to be involved in the bridging of membrane vesicles and trafficking of proteins to the plasma membrane. All three proteins co‐localize at the intracellular face of the plasma membrane in a Ca2+‐dependent manner. The binding of AHNAK to (p11)2(AnxA2)2 has been studied previously, and a minimal binding motif has been mapped to a 20‐amino‐acid peptide corresponding to residues 5654–5673 of the AHNAK C‐terminal domain. Here, the 2.5 Å resolution crystal structure of this 20‐amino‐acid peptide of AHNAK bound to the AnxA2–S100A10 heterotetramer (1:2:2 symmetry) is presented, which confirms the asymmetric arrangement first described by Rezvanpour and coworkers and explains why the binding motif has high affinity for (p11)2(AnxA2)2. Binding of AHNAK to the surface of (p11)2(AnxA2)2 is governed by several hydrophobic interactions between side chains of AHNAK and pockets on S100A10. The pockets are large enough to accommodate a variety of hydrophobic side chains, allowing the consensus sequence to be more general. Additionally, the various hydrogen bonds formed between the AHNAK peptide and (p11)2(AnxA2)2 most often involve backbone atoms of AHNAK; as a result, the side chains, particularly those that point away from S100A10/AnxA2 towards the solvent, are largely interchangeable. While the structure‐based consensus sequence allows interactions with various stretches of the AHNAK C‐terminal domain, comparison with other S100 structures reveals that the sequence has been optimized for binding to S100A10. This model adds new insight to the understanding of the specific interactions that occur in this membrane‐repair scaffold.

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AHNAK2 Participates in the Stress‐Induced Nonclassical FGF1 Secretion Pathway

Kirov

Kacer

Conley

et al. 2015

J of Cellular Biochemistry

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FGF1 is a nonclassically released growth factor that regulates carcinogenesis, angiogenesis and inflammation. In vitro and in vivo, FGF1 export is stimulated by cell stress. Upon stress, FGF1 is transported to the plasma membrane where it localizes prior to transmembrane translocation. To determine which proteins participate in the submembrane localization of FGF1 and its export, we used immunoprecipitation mass spectrometry to identify novel proteins that associate with FGF1 during heat shock. The heat shock-dependent association of FGF1 with the large protein AHNAK2 was observed. Heat shock induced the translocation of FGF1 and AHNAK2 to the cytoskeletal fraction. In heat-shocked cells, FGF1 and the C-terminal fragment of AHNAK2 colocalized with F-actin in the vicinity of the cell membrane. Depletion of AHNAK2 resulted in a drastic decrease of stress-induced FGF1 export but did not affect spontaneous FGF2 export and FGF1 release induced by the inhibition of Notch signaling. Thus, AHNAK2 is an important element of the FGF1 nonclassical export pathway.

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Identification of an AHNAK Binding Motif Specific for the Annexin2/S100A10 Tetramer

Cited by 37 publications

References 49 publications

Contribution of Annexin 2 to the Architecture of Mature Endothelial Adherens Junctions

Contribution of Annexin 2 to the Architecture of Mature Endothelial Adherens Junctions

Structure of a C-terminal AHNAK peptide in a 1:2:2 complex with S100A10 and an acetylated N-terminal peptide of annexin A2

AHNAK2 Participates in the Stress‐Induced Nonclassical FGF1 Secretion Pathway

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