Drebrin, an actin‐binding protein, is required for lens morphogenesis and growth

Abstract

Background: Lens morphogenesis, architecture, and clarity are known to be critically dependent on actin cytoskeleton organization and cell adhesive interactions. There is limited knowledge, however regarding the identity and role of key proteins regulating actin cytoskeletal organization in the lens. This study investigated the role of drebrin, a developmentally regulated actinbinding protein, in mouse lens development by generating and characterizing a conditional knockout (cKO) mouse model using the Cre-LoxP recombination approach. Results: Drebrin E, a splice variant of DBN1 is a predominant isoform expressed in the mouse lens and exhibits a maturation-dependent downregulation. Drebrin co-distributes with actin in both epithelium and fibers.Conditional deficiency (both haploinsufficiency and complete absence) of drebrin results in disrupted lens morphogenesis leading to cataract and microphthalmia. The drebrin cKO lens reveals a dramatic decrease in epithelial height and width, E-cadherin, and proliferation, and increased apoptotic cell death and expression of α-smooth muscle actin, together with severely impaired fiber cell organization, polarity, and cell-cell adhesion.Conclusions: This study demonstrates the requirement of drebrin in lens development and growth, with drebrin deficiency leading to impaired lens morphogenesis and microphthalmia.

Aberrant expression of COL4A1 in age-related cataract and its effect on cell proliferation, apoptosis and gene expression changes

“…The cytoskeleton is a complex network consisting of three major filament systems: microfilaments, microtubules and intermediate filaments [21] . Cytoskeleton is most well-known for its importance to the lens [22] . Ultraviolet radiation, aging, hypoxia, and other stimuli could cause excess apoptosis of lens epithelial cells, thus causing cytoskeletal degradation, accumulation of crystal protein, and ultimately cataract [23] .…”