Deletion of beaded filament proteins or the C-terminal end of Aquaporin 0 causes analogous abnormal distortion aberrations in mouse lens

Insights into the biochemical and biophysical mechanisms mediating the longevity of the transparent optics of the eye lens

“…In addition to this structural function, one of the lens intermediate filament proteins, the beaded filament structural protein 1 (BFSP1, aka filensin) regulates the activity of the major lens fiber cell water channel, aquaporin 0 (AQP0; (363)(364)(365)). It therefore directly regulates the optical properties of the lens (see later).…”

“…BFSP1 is therefore directly involved in regulating water transport in the lens (363,387). Indeed, the genetic removal of either beaded filaments or AQP0 phenocopy each other (365). The AQP0-beaded filament complex also affects connexin function (364), indicating that the beaded filament cytoskeleton along with water and ion channels is directly involved in the lens microcirculation system (48, 262) to regulate transparency and optical function (366,369).…”

Independent Membrane Binding Properties of the Caspase Generated Fragments of the Beaded Filament Structural Protein 1 (BFSP1) Involves an Amphipathic Helix

“…Then the process of lens fibre cell compaction [ 79 ] and the fenestration of lens fibre cells leading to the formation of a stratified syncytium [ 80 ] will require an amphipathic helix containing proteins to be involved. Epitope mapping of bovine BFSP1 showed that the very C-terminal region becomes concentrated on the cell membranes in the bovine lens nucleus [ 24 ], which in the context of the data presented here, provides a different perspective on how beaded filaments and aquaporins affect the optical properties of the lens [ 18 , 33 , 81 ].…”

“…The site was identified after tryptic digestion of the cross-linked sample. This demonstrates that BFSP1 binds the C-terminal region of AQP0, a domain that is crucial to its water channel regulation [ 32 , 33 ]. This observation implies that AQP0 could facilitate the binding of BFSP1 [ 20 , 24 , 26 , 34 , 35 ] and its myristoylated fragments [ 18 ] to the lens fibre cell plasma membranes.…”

Prevention of age-related truncation of γ-glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation

“…Dark-field images of the lens were acquired in accordance with the methods described in a previous publication ( 81 ). For lens grid view microscopy, we followed the procedures outlined in another prior publication ( 82 ). Briefly, the lenses were incubated in prewarmed Hanks’ balanced salt solution.…”