| First Author | Baudier J | Year | 2018 |
| Journal | J Cell Sci | Volume | 131 |
| Issue | 8 | PubMed ID | 29654161 |
| Mgi Jnum | J:261663 | Mgi Id | MGI:6151363 |
| Doi | 10.1242/jcs.213959 | Citation | Baudier J, et al. (2018) The filamin-B-refilin axis - spatiotemporal regulators of the actin-cytoskeleton in development and disease. J Cell Sci 131(8):jcs213959 |
| abstractText | 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-beta 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-beta 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. |
