Myxoma viral serpin, Serp-1, inhibits human monocyte adhesion through regulation of actin-binding protein filamin B

FILAMIN B, which encodes a cytoplasmic actin binding protein, is mutated in several skeletal dysplasias. To further investigate how an actin binding protein influences skeletogenesis, we generated mice lacking intact Filamin B. As observed in spondylocarpotarsal synostosis syndrome patients, Filamin B mutant mice display ectopic mineralization in many cartilaginous elements. This aberrant mineralization is due to ectopic chondrocyte hypertrophy similar to that seen in mice expressing Runx2 in chondrocytes. Accordingly, removing one copy of Runx2 rescues the Filamin B mutant phenotype, indicating that Filamin B is a regulator of Runx2 function during chondrocyte differentiation. Filamin B binds Smad3, which is known to interact with Runx2. Smad3 phosphorylation is increased in the mutant mice. Thus, Filamin B inhibits Runx2 activity, at least in part, through the Smad3 pathway. Our results uncover the involvement of actin binding proteins during chondrogenesis and provide a molecular basis to a human genetic disease.

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Clathrin Hub Expression Dissociates the Actin-Binding Protein Hip1R from Coated Pits and Disrupts Their Alignment with the Actin Cytoskeleton

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10.1034/j.1600-0854.2001.21114.x ◽

2001 ◽

Vol 2 (11) ◽

pp. 851-858 ◽

Cited By ~ 31

Author(s):

Elizabeth M. Bennett ◽

Chih-Ying Chen ◽

Asa E. Y. Engqvist-Goldstein ◽

David G. Drubin ◽

Frances M. Brodsky

Keyword(s):

Actin Cytoskeleton ◽

Binding Protein ◽

Actin Binding ◽

Coated Pits ◽

Actin Binding Protein

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The actin binding protein villin controls accessibility of insulin granules to their docking sites

10.1055/s-0038-1641805 ◽

2018 ◽

Author(s):

H Mziaut ◽

J Dehghany ◽

M Meyer-Hermann ◽

M Solimena

Keyword(s):

Binding Protein ◽

Actin Binding ◽

Actin Binding Protein ◽

Insulin Granules ◽

Docking Sites

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Binding of Human Platelet Glycoprotein lb and Actin to Fragments of Actin-Binding Protein

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648421 ◽

1992 ◽

Vol 67 (02) ◽

pp. 252-257 ◽

Cited By ~ 9

Author(s):

Anne M Aakhus ◽

J Michael Wilkinson ◽

Nils Olav Solum

Keyword(s):

Actin Filaments ◽

High Speed ◽

Binding Protein ◽

Protein A ◽

Actin Binding ◽

Platelet Glycoprotein ◽

Actin Binding Protein ◽

Crossed Immunoelectrophoresis ◽

Triton X ◽

Calpain Inhibitors

SummaryActin-binding protein (ABP) is degraded into fragments of 190 and 90 kDa by calpain. A monoclonal antibody (MAb TI10) against the 90 kDa fragment of ABP coprecipitated with the glycoprotein lb (GP lb) peak observed on crossed immunoelectrophoresis of Triton X-100 extracts of platelets prepared without calpain inhibitors. MAb PM6/317 against the 190 kDa fragment was not coprecipitated with the GP lb peak under such conditions. The 90 kDa fragment was adsorbed on protein A agarose from extracts that had been preincubated with antibodies to GP lb. This supports the idea that the GP Ib-ABP interaction resides in the 90 kDa region of ABP. GP lb was sedimented with the Triton-insoluble actin filaments in trace amounts only, and only after high speed centrifugation (100,000 × g, 3 h). Both the 190 kDa and the 90 kDa fragments of ABP were sedimented with the Triton-insoluble actin filaments.

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