FilaminB is required for the directed localization of cell–cell adhesion molecules in embryonic epithelial development

Abstract

Filamin proteins cross-link F-actin and form a scaffold for numerous signal transduction systems. In this study, we show that filaminB is apically enriched in avian embryonic epithelium, and colocalizes with cell adhesion molecules and circumferential F-actin. FilaminB knockdown in the neural tube and somites decreases the accumulation of N-cadherin and ZO-1 protein at cell junctions, and promotes disruption of these tissues and the presence of neuronal aggregates within the lumen of the neural tube. This phenotype resembles that of human congenital condition, periventricular heterotopia (PH). FilaminB knockdown in MDCK cells suggests that filaminB is required for the apical accumulation of adhesion molecules in the junctional complex and subsequent epithelium formation. We further suggest that the reduction of structural integrity of the neural epithelium caused by the loss of Filamin function may also result in formation of the neuronal nodules found in PH patients. Developmental Dynamics 240:149-161,

Spatial integration of E-cadherin adhesion, signalling and the epithelial cytoskeleton

“…The F-actin bundling and cross-linking proteins -actinin 4 [37] and filaminA/B localise at cell-cell contacts are essential for cadherin adhesion in different tissues [38][39][40]. At junctions, filaminA and filaminB are known to fine tune activation of RhoA and Rac1 via binding to the GEF Trio or the GAP FilGAP, respectively [38,41].…”

Cadherin adhesome at a glance

“…Once several F-actin filaments are polymerized, they can be arranged into different higher-level structures, and connect with the AJs through different actin-binding adaptors. The cadhesome contains several actin cross-linking proteins, such as a-actinin and filamin, and several myosin motors that can serve as cross linkers as well as force-generating machines (Knudsen et al, 1995;Maddugoda et al, 2007;Smutny et al, 2010;Wakamatsu et al, 2011).…”

Cell Polarity 1

“…Knockout mice lacking filamin A and filamin B exhibit poor development of blood vessels, possibly due to impairments in cell-cell adhesion and migration of endothelial cells Zhou et al 2007). The consequences of filamin B knockdown in MDCK cells suggest that this protein is required for the accumulation of adhesion molecules in the junctional complexes and subsequent formation of an epithelium (Wakamatsu et al 2011). Thus, JRAB/ MICAL-L2 may regulate cell-cell adhesion through interaction of filamins in epithelial cells, although the precise mechanism remains unknown.…”