Lens intermediate filaments

Abstract

The ocular lens assembles two separate Intermediate Filament systems sequentially with differentiation. Canonical 8-11 nm IFs composed of Vimentin are assembled in lens epithelial cells and younger fiber cells, while the fiber cell-specific Beaded Filaments are switched on as fiber cell elongation initiates. Some of the key features of both filament systems are reviewed.Actin filaments and microtubules are essential to the most elemental functions of eukaryotic cells. These filamentous structures are assembled from proteins derived from small, highly conserved gene families. Though tissue specificity exists in the expression of some actin and tubulin family members, they are generally expressed in a ubiquitous manner, and are required for eukaryotic cell survival and replication. In contrast, the family of proteins that comprise the cytoplasmic Intermediate Filaments (IFs) is one of the largest in the human genome with greater than 60 members. IFs are generally not required for cell survival, and are absent from single cell eukaryotes, suggesting a more recent appearance on the evolutionary stage, and a less-essential role in the biology of the cell.The IF family also differs sharply from actins and tubulins in that there is great variation in both size and sequence among the IF proteins, with sequence identity falling below 30% between more distant members of the human IF family. However, despite the large number of IF proteins available for the construction of IFs, any given cell typically expresses only 1-3 IF proteins, with expression tightly restricted to cell type and state of differentiation. This suggests a considerable degree of cell-specific specialization.While IF proteins show considerable sequence and size variation, they are unified into a family on the basis of three major features:1. Predicted domain structure (see figure 1): Algorithms that predict coiled-coil structure show a common predicted domain structure consisting of a) head and tail domains which are quite variable in both size and sequence, and b) a central rod domain where the size (~310 amino acids) and predicted secondary structure is strongly conserved. The rod domain consists of large regions of alpha helical structure (coil domains) interrupted by short non-helical regions ("linkers") that connect the coil domains. The size, number, and placement of linkers and coils are well-conserved. Moreover, the coil domains exhibit a heptad repeat pattern where the 1, 4 positions in the heptad are dominated by hydrophobic amino acids. Because the 1,4 positions are aligned on one

Intact and N- or C-terminal end truncated AQP0 function as open water channels and cell-to-cell adhesion proteins: End truncation could be a prelude for adjusting the refractive index of the lens to prevent spherical aberration

“…However, the possible purpose or the mechanism behind this lens barrier development in the inner cortex [74] remains unknown. Based on our present and previously published data (2,15,47] as well as inferring from reports on observations by other investigators [70,71,75–77,79,83–85,106,120], we hypothesize the following: The constantly growing lens has to adjust and maintain the increasing refractive index gradient, from the cortex to the nucleus, for proper focusing. To increase the refractive index, a gradual reduction in the extracellular space as well as removal of water content from both the extracellular space and cytoplasm of the mature fiber cells occur in the inner cortex and nucleus.…”

“…The remarkable cellular rearrangements that occur in the mature fiber cells in the inner cortex and nucleus most probably could be due to dissociation of cytoplasmic N- and C-terminal ends of membrane proteins like AQP0, connexins etc., from the cytosolic proteins like crystallins and lens-specific cytoskeletal beaded filament proteins such as filensin and CP49. In order to adjust the refractive index and reduce diffraction of light in the ocular lens, fiber cells undergo a unique process of maturation by losing their nuclei as well as eliminating cellular organelles and cytoskeletal proteins; actins, intermediate filaments and beaded filaments filensin and CP49 are absent in the lens nucleus [90–106]. Blankenship et al [105] showed that filensin rod domain and phakinin (CP49) localized at the membrane lining region in outer cortex cells and to the central region of the cytoplasm in inner cortex cells.…”

Altered ubiquitin causes perturbed calcium homeostasis, hyperactivation of calpain, dysregulated differentiation, and cataract

“…Filensin and Vimentin are major components of the intermediate filaments of the lens cytoskeleton (43). Fodrin is important in cell membrane (44).…”

Role of Aquaporin 0 in lens biomechanics

“…The specialized intermediate BF cytoskeletal network is tethered to the fiber cell plasma membranes [28]. Targeted deletion of BF protein CP49 or filensin caused a dramatic loss of the highly ordered architecture of the lens [29–32].…”