Bridging integrator protein 3 (Bin3) deletion causes cataract due to morphological abnormalities in lens cells

Abstract

The lens is a complex epithelial tissue whose highly organized structure is required for its transparency. The BAR superfamily of peripheral membrane proteins control membrane curvature in many contexts and deletion of the BAR family member, Bin3, from mice results in cataracts (a clouding of the lens) associated with actin defects. However, the role that Bin3 plays in postnatal lens development and homeostasis is not known.Hematoxylin and Eosin staining of Bin3 null lenses revealed minor defects in fiber cell packing from birth to 3 weeks postnatal. The defects in fiber cell packing became progressively worse from 1 month until the fiber cells exhibited both vacuoles and disrupted fiber cell packing by 2 months. Scanning electron micrographs show that the elaborate membrane protrusions found on normal lens fiber cells becomes disorganized in Bin3 null lenses. The observed actin defects along with the morphological defect lead us to hypothesize that Bin3 is important for actin nucleation along lens fiber cell lateral membranes. Multiple proteins such as Cdc42, N‐WASP, and ARP2/3 control actin nucleation. In yeast Bin3 recruits Cdc42 to the cell division site and facilitates its activation, thus changing the cytoskeleton. It has not been shown whether this process is conserved in mammalian cells. Current studies suggest that Cdc42 plays a role in changing the cytoskeleton in Bin3 null lenses.Funded by NEI EY12221.Grant Funding Source: NEI EY 12221