Human β-Filamin Is a New Protein That Interacts with the Cytoplasmic Tail of Glycoprotein Ibα

Takafuta, Toshiro; Wu, Guoxin; Murphy, Gëorge F.; Shapiro, Sandor S.

doi:10.1074/jbc.273.28.17531

Cited by 105 publications

(103 citation statements)

References 47 publications

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“…Flna is one of three filamin isoforms essential for normal development in humans (6,9,20,21). Flnb has some overlapping expression with Flna and could provide functional redundancy in some cell types (22,23). Although Flnc is fairly specific to muscle cells (24), it expresses in some nonmuscle cells during development (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Filamin A (FLNA) is required for cell–cell contact in vascular development and cardiac morphogenesis

Feng

Chen

Moskowitz

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

271

257

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Mutations in the human Filamin A (FLNA) gene disrupt neuronal migration to the cerebral cortex and cause cardiovascular defects. Complete loss of Flna in mice results in embryonic lethality with severe cardiac structural defects involving ventricles, atria, and outflow tracts, as well as widespread aberrant vascular patterning. Despite these widespread developmental defects, migration and motility of many cell types does not appear to be affected. Instead, Flna-null embryos display abnormal epithelial and endothelial organization and aberrant adherens junctions in developing blood vessels, heart, brain, and other tissues. Essential roles for FLNA in intercellular junctions provide a mechanism for the diverse developmental defects seen in patients with FLNA mutations.adherens junctions ͉ cardiovascular morphogenesis ͉ angiogenesis ͉ neural crest ͉ neuronal migration

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Section: Discussionmentioning

confidence: 99%

Filamin A (FLNA) is required for cell–cell contact in vascular development and cardiac morphogenesis

Feng

Chen

Moskowitz

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

271

257

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“…Western blotting was performed as described (26). The blots were incubated with polyclonal rabbit anti-filamin B antibody (17) …”

Section: Western Blottingmentioning

confidence: 99%

“…Tissue Immunofluorescence-Cryopreserved sections of mouse tissue were analyzed for filamin B (polyclonal rabbit antibody) (17), filamin A (monoclonal mouse antibody, Chemicon), PECAM/CD31 (monoclonal rat antibody, BD Pharmingen), von Willebrand factor (polyclonal rabbit antibody, Dako), and ␣-smooth muscle actin (polyclonal rabbit antibody, LabVision). Primary antibodies were incubated overnight at 4°C (1:50).…”

Section: Immunofluorescence Studiesmentioning

confidence: 99%

“…Three filamins have been described: filamin A, or ABP280, is the most abundant and is widely expressed in different tissues; filamin B is also broadly expressed; and filamin C is mainly expressed in skeletal muscle (12)(13)(14). High levels of filamin A and filamin B have previously been detected in vessels (15)(16)(17) and in endothelial cells in culture (17)(18)(19). Knock-out experiments show the functional importance of each isoform: filamin A knock-out mice die during development due to aberrant vascular patterning and cardiac defects (20,21), whereas filamin B deficiency in mice mainly causes skeletal malformations (22)(23)(24) and vascular deficiencies (23).…”

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confidence: 99%

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Filamin B Plays a Key Role in Vascular Endothelial Growth Factor-induced Endothelial Cell Motility through Its Interaction with Rac-1 and Vav-2

Valle-Pérez

Martínez

Lacasa-Salavert

et al. 2010

Journal of Biological Chemistry

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“…FLNB was first isolated as a protein that interacts with the cytoplasmic tail of glycoprotein Ib␣ (4,5). The 2,603-aa chain of FLNB contains an amino-terminal actin-binding domain and a backbone of 24 Ig-like rod domain repeats disrupted by two hinge regions (6).…”

mentioning

confidence: 99%

Filamin B deficiency in mice results in skeletal malformations and impaired microvascular development

Zhou

Tian²,

Sandzén³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

116

100

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Mutations in filamin B (FLNB), a gene encoding a cytoplasmic actin-binding protein, have been found in human skeletal disorders, including boomerang dysplasia, spondylocarpotarsal syndrome, Larsen syndrome, and atelosteogenesis phenotypes I and III. To examine the role of FLNB in vivo, we generated mice with a targeted disruption of Flnb. Fewer than 3% of homozygous embryos reached term, indicating that Flnb is important in embryonic development. Heterozygous mutant mice were indistinguishable from their wild-type siblings. Flnb was ubiquitously expressed; strong expression was found in endothelial cells and chondrocytes. Flnb-deficient fibroblasts exhibited more disorganized formation of actin filaments and reduced ability to migrate compared with wild-type controls. Flnb-deficient embryos exhibited impaired development of the microvasculature and skeletal system. The few Flnb-deficient mice that were born were very small and had severe skeletal malformations, including scoliotic and kyphotic spines, lack of intervertebral discs, fusion of vertebral bodies, and reduced hyaline matrix in extremities, thorax, and vertebrae. These mice died or had to be euthanized before 4 weeks of age. Thus, the phenotypes of Flnb-deficient mice closely resemble those of human skeletal disorders with mutations in FLNB.chondrocytes ͉ endothelial cell ͉ gene targeting F ilamins are large actin-binding proteins that stabilize the actin cytoskeleton, link the actin network with cellular membranes, and mediate interactions between actin and transmembrane receptors (1). In mouse, there are three filamin genes, Flna, Flnb, and Flnc. Flna and Flnb, which encode large proteins with 70% structural similarity, are ubiquitously expressed, whereas Flnc, encoding a much smaller protein, is expressed in heart and skeletal muscles. It has been proposed that filamins are important for fetal development by regulating the communication between extracellular signals and the cellular cytoskeleton to guide migration of cells into appropriate anatomical sites (1). In addition to actin, filamins are capable of binding to a wide range of molecules involved in cellular signaling and transcriptional regulation (2, 3).FLNB was first isolated as a protein that interacts with the cytoplasmic tail of glycoprotein Ib␣ (4, 5). The 2,603-aa chain of FLNB contains an amino-terminal actin-binding domain and a backbone of 24 Ig-like rod domain repeats disrupted by two hinge regions (6). Mouse Flnb is located on chromosome 14 and consists of 47 exons. In mouse embryos, Flnb is expressed in vertebral bodies, and it has been suggested that Flnb may play a role in vertebral segmentation, joint formation, and endochondral ossification (7).Mutations in the human FLNB gene have been found in several skeletal disorders, including spondylocarpotarsal syndrome, autosomal-dominant Larsen syndrome, atelosteogenesis I and III (7), and boomerang dysplasia (8). The skeletal disorders caused by mutations in FLNB are very similar to those caused by mutations in FLNA (9). Interesting...

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Human β-Filamin Is a New Protein That Interacts with the Cytoplasmic Tail of Glycoprotein Ibα

Cited by 105 publications

References 47 publications

Filamin A (FLNA) is required for cell–cell contact in vascular development and cardiac morphogenesis

Filamin A (FLNA) is required for cell–cell contact in vascular development and cardiac morphogenesis

Filamin B Plays a Key Role in Vascular Endothelial Growth Factor-induced Endothelial Cell Motility through Its Interaction with Rac-1 and Vav-2

Filamin B deficiency in mice results in skeletal malformations and impaired microvascular development

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