Periaxin is required for hexagonal geometry and membrane organization of mature lens fibers

Abstract

Transparency of the ocular lens depends on symmetric packing and membrane organization of highly elongated hexagonal fiber cells. These cells possess an extensive, well-ordered cortical cytoskeleton to maintain cell shape and to anchor membrane components. Periaxin (Prx), a PDZ domain protein involved in myelin sheath stabilization, is also a component of adhaerens plaques in lens fiber cells. Here we show that Prx is expressed in lens fibers and exhibits maturation dependent redistribution, clustering discretely at the tricellular junctions in mature fiber cells. Prx exists in a macromolecular complex with proteins involved in membrane organization including ankyrin-B, spectrin, NrCAM, filensin, ezrin and desmoyokin. Importantly, Prx knockout mouse lenses were found to be softer and more easily deformed than normal lenses, revealing disruptions in fiber cell hexagonal packing, membrane skeleton and membrane stability. These observations suggest a key role for Prx in maturation, packing, and membrane organization of lens fiber cells. Hence, there may be functional parallels between the roles of Prx in membrane stabilization of the myelin sheath and the lens fiber cell.

The role of calcium-independent phospholipase A2γ in modulation of aqueous humor drainage and Ca2+ sensitization of trabecular meshwork contraction

“…Tissue sections from formalin-fixed, paraffin-embedded human donor eye whole globes were immunostained as previously described (30). Briefly, five-micron thick tissue sections were deparaffinized and rehydrated using three changes of xylene, followed by three changes of absolute ethyl alcohol and washing with three changes of water.…”

Tropomodulin 1 Constrains Fiber Cell Geometry during Elongation and Maturation in the Lens Cortex

“…Abnormal fiber cell shapes and qualitative loss of hexagonal packing geometry have also been observed in lenses from mice with targeted deletions in the axon guidance molecules, ephrin-A5 ligand (Cooper et al 2008) and EPHA2 receptor (Jun et al 2009), the beaded filament proteins, CP49 and filensin (Sandilands et al 2003;Yoon et al 2008), and the cytoskeletal scaffolding protein, periaxin (Maddala et al 2011). In the case of ephrin-A5-or EPHA2-null mice, abnormal fiber cell shapes and disordered packing are evident in young fiber cells likely still in the process of elongation, similar to Tmod1-null lenses (Cooper et al 2008;Jun et al 2009).…”

Periaxin and AHNAK Nucleoprotein 2 Form Intertwined Homodimers through Domain Swapping

“…Interestingly, PRX is also required for the hexagonal packing of lens fibers (11). The domain organization of PRX and AHNAKs, as well as the structures of their dimerization domains, may be signs of these proteins being involved in macromolecular complexes with similar assembly pathways (57).…”

“…Genetic defects in PRX result in demyelinating peripheral neuropathies, such as Charcot-Marie-Tooth and Dejerine-Sottas diseases, indicating a crucial role for PRX in the normal development of the peripheral nervous system (8 -10). PRX is also a member of cytoskeletal complexes in lens fibers, and it is considered to function in maturation, packing, and membrane organization of lens fiber cells (11).…”