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Actin-tethered junctional complexes in angiogenesis and lymphangiogenesis in association with vascular endothelial growth factor.

Zankov DP, Ogita H - Biomed Res Int (2015)

Bottom Line: Here we review involvement of actin cytoskeleton-associated junctional molecules of endothelial cells in angiogenesis and lymphangiogenesis.Particularly, we focus on F-actin binding protein afadin, an adaptor protein involved in broad range of signaling mechanisms.We propose that targeting actin-tethered junctional molecules, including afadin, may present a new approach to angiogenic therapy that in combination with today used medications like VEGF inhibitors will benefit against development of pathological angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Seta Tsukinowa-cho, Shiga, Otsu 520-2192, Japan.

ABSTRACT
Vasculature is present in all tissues and therefore is indispensable for development, biology, and pathology of multicellular organisms. Endothelial cells guarantee proper function of the vessels and are the original component in angiogenesis. Morphogenesis of the vascular system utilizes processes like cell adhesion, motility, proliferation, and survival that are closely related to the dynamics of actin filaments and actin-tethered adhesion complexes. Here we review involvement of actin cytoskeleton-associated junctional molecules of endothelial cells in angiogenesis and lymphangiogenesis. Particularly, we focus on F-actin binding protein afadin, an adaptor protein involved in broad range of signaling mechanisms. Afadin mediates the pathways of vascular endothelial growth factor- (VEGF-) and sphingosine 1-phosphate-triggered angiogenesis and is essential for embryonic development of lymph vessels in mice. We propose that targeting actin-tethered junctional molecules, including afadin, may present a new approach to angiogenic therapy that in combination with today used medications like VEGF inhibitors will benefit against development of pathological angiogenesis.

No MeSH data available.


Related in: MedlinePlus

Anatomy of afadin molecule. The modular structure of l-afadin (a) and s-afadin (b) is schematically shown. Numbers in parentheses indicate the first and last amino acid of the structural domains. RA: Ras associated domain; FHA: forkhead associated domain; DIL: dilute domain; PDZ: postsynaptic density, Drosophila disk large tumor suppressor, zonula occludens-1 domain; PR: proline rich domain; F-actin: F-actin binding domain. PDZ domain interacts with nectin molecules.
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fig1: Anatomy of afadin molecule. The modular structure of l-afadin (a) and s-afadin (b) is schematically shown. Numbers in parentheses indicate the first and last amino acid of the structural domains. RA: Ras associated domain; FHA: forkhead associated domain; DIL: dilute domain; PDZ: postsynaptic density, Drosophila disk large tumor suppressor, zonula occludens-1 domain; PR: proline rich domain; F-actin: F-actin binding domain. PDZ domain interacts with nectin molecules.

Mentions: Afadin is an adaptor protein discovered in 1997 by Mandai et al. and holds two RA (Ras association), a FHA (forkhead-associated), a DIL (dilute), a PDZ (postsynaptic density, Drosophila disk large tumor suppressor, zonula occludens-1), three PR (proline-rich), and F-actin structural domains (Figure 1) [20]. Two isoforms are described at present: l-afadin and s-afadin. s-Afadin truncates the C-terminal F-actin and the third PR domains. l-Afadin is expressed ubiquitously, whereas s-afadin is expressed mainly in the nerve tissue [21]. F-actin and PDZ domains link actin filaments and Ig-like transmembrane junctional proteins nectins, respectively. Resulting cell-cell adhesion assembly is crucial for establishment and part of adherens and tight junctions in epithelia, fibroblasts, and ECs [15, 22]. In addition, afadin functions independently of nectins to promote cell movement and neuronal physiology [23–26]. Due to the multitude of interacting domains and fundamental role of cell-cell junctions for tissue organization [27], afadin is involved in various biological phenomena ranging from embryonic development to cancer progression. Complexity of those processes creates a broad field of constantly increasing information of afadin roles [28–32].


Actin-tethered junctional complexes in angiogenesis and lymphangiogenesis in association with vascular endothelial growth factor.

Zankov DP, Ogita H - Biomed Res Int (2015)

Anatomy of afadin molecule. The modular structure of l-afadin (a) and s-afadin (b) is schematically shown. Numbers in parentheses indicate the first and last amino acid of the structural domains. RA: Ras associated domain; FHA: forkhead associated domain; DIL: dilute domain; PDZ: postsynaptic density, Drosophila disk large tumor suppressor, zonula occludens-1 domain; PR: proline rich domain; F-actin: F-actin binding domain. PDZ domain interacts with nectin molecules.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4389985&req=5

fig1: Anatomy of afadin molecule. The modular structure of l-afadin (a) and s-afadin (b) is schematically shown. Numbers in parentheses indicate the first and last amino acid of the structural domains. RA: Ras associated domain; FHA: forkhead associated domain; DIL: dilute domain; PDZ: postsynaptic density, Drosophila disk large tumor suppressor, zonula occludens-1 domain; PR: proline rich domain; F-actin: F-actin binding domain. PDZ domain interacts with nectin molecules.
Mentions: Afadin is an adaptor protein discovered in 1997 by Mandai et al. and holds two RA (Ras association), a FHA (forkhead-associated), a DIL (dilute), a PDZ (postsynaptic density, Drosophila disk large tumor suppressor, zonula occludens-1), three PR (proline-rich), and F-actin structural domains (Figure 1) [20]. Two isoforms are described at present: l-afadin and s-afadin. s-Afadin truncates the C-terminal F-actin and the third PR domains. l-Afadin is expressed ubiquitously, whereas s-afadin is expressed mainly in the nerve tissue [21]. F-actin and PDZ domains link actin filaments and Ig-like transmembrane junctional proteins nectins, respectively. Resulting cell-cell adhesion assembly is crucial for establishment and part of adherens and tight junctions in epithelia, fibroblasts, and ECs [15, 22]. In addition, afadin functions independently of nectins to promote cell movement and neuronal physiology [23–26]. Due to the multitude of interacting domains and fundamental role of cell-cell junctions for tissue organization [27], afadin is involved in various biological phenomena ranging from embryonic development to cancer progression. Complexity of those processes creates a broad field of constantly increasing information of afadin roles [28–32].

Bottom Line: Here we review involvement of actin cytoskeleton-associated junctional molecules of endothelial cells in angiogenesis and lymphangiogenesis.Particularly, we focus on F-actin binding protein afadin, an adaptor protein involved in broad range of signaling mechanisms.We propose that targeting actin-tethered junctional molecules, including afadin, may present a new approach to angiogenic therapy that in combination with today used medications like VEGF inhibitors will benefit against development of pathological angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Seta Tsukinowa-cho, Shiga, Otsu 520-2192, Japan.

ABSTRACT
Vasculature is present in all tissues and therefore is indispensable for development, biology, and pathology of multicellular organisms. Endothelial cells guarantee proper function of the vessels and are the original component in angiogenesis. Morphogenesis of the vascular system utilizes processes like cell adhesion, motility, proliferation, and survival that are closely related to the dynamics of actin filaments and actin-tethered adhesion complexes. Here we review involvement of actin cytoskeleton-associated junctional molecules of endothelial cells in angiogenesis and lymphangiogenesis. Particularly, we focus on F-actin binding protein afadin, an adaptor protein involved in broad range of signaling mechanisms. Afadin mediates the pathways of vascular endothelial growth factor- (VEGF-) and sphingosine 1-phosphate-triggered angiogenesis and is essential for embryonic development of lymph vessels in mice. We propose that targeting actin-tethered junctional molecules, including afadin, may present a new approach to angiogenic therapy that in combination with today used medications like VEGF inhibitors will benefit against development of pathological angiogenesis.

No MeSH data available.


Related in: MedlinePlus