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• W2797154802 abstract "ABSTRACT During development, cycles of spatiotemporal remodeling of higher-order networks of actin filaments contribute to control cell fate specification and differentiation. Programs for controlling these dynamics are hard-wired into actin-regulatory proteins. The filamin family of actin-binding proteins exert crucial mechanotransduction and signaling functions in tissue morphogenesis. Filamin-B (FLNB) is a key player in chondrocyte progenitor differentiation for endochondral ossification. Biallelic loss-of-function mutations or gain-of-function mutations in FLNB cause two groups of skeletal disorders that can be attributed to either the loss of repressive function on TGF-β signaling or a disruption in mechanosensory properties, respectively. In this Review, we highlight a unique family of vertebrate-specific short-lived filamin-binding proteins, the refilins (refilin-A and refilin-B), that modulate filamin-dependent actin crosslinking properties. Refilins are downstream TGF-β effectors in epithelial cells. Double knockout of both refilin-A and refilin-B in mice results in precocious ossification of some axial skeletal elements, leading to malformations that are similar to those seen in FLNB-deficient mice. Based on these findings, we present a model summarizing the role of refilins in regulating the mechanosensory functions of FLNB during skeletal development. We also discuss the possible contribution of refilins to FLNB-related skeletal pathologies that are associated with gain-of-function mutations." @default.
• W2797154802 created "2018-04-24" @default.
• W2797154802 creator A5022062950 @default.
• W2797154802 creator A5052568711 @default.
• W2797154802 creator A5059069293 @default.
• W2797154802 date "2018-04-13" @default.
• W2797154802 modified "2023-10-15" @default.
• W2797154802 title "The filamin-B–refilin axis – spatiotemporal regulators of the actin-cytoskeleton in development and disease" @default.
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• W2797154802 doi "https://doi.org/10.1242/jcs.213959" @default.
• W2797154802 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29654161" @default.
• W2797154802 hasPublicationYear "2018" @default.
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