First Author | Maddala R | Year | 2017 |
Journal | Invest Ophthalmol Vis Sci | Volume | 58 |
Issue | 9 | Pages | 3445-3455 |
PubMed ID | 28692740 | Mgi Jnum | J:258447 |
Mgi Id | MGI:6112193 | Doi | 10.1167/iovs.17-21539 |
Citation | Maddala R, et al. (2017) Switching of alpha-Catenin From Epithelial to Neuronal Type During Lens Epithelial Cell Differentiation. Invest Ophthalmol Vis Sci 58(9):3445-3455 |
abstractText | Purpose: Ocular lens fiber cell elongation, differentiation, and compaction are associated with extensive reorganization of cell adhesive interactions and cytoskeleton; however, our knowledge of proteins critical to these events is still evolving. This study characterizes the distribution pattern of neuronal-specific alpha-catenin (alphaN-catenin) and its interaction with the N-cadherin-associated adherens junctions (AJs) and their stability in the mouse lens fibers. Methods: Expression and distribution of alphaN-catenin in developing mouse and adult human lenses was determined by RT-PCR, immunoblot, and immunofluorescence analyses. Characterization of alphaN-catenin and N-cadherin interacting proteins and colocalization analyses were performed using immunoprecipitation, mass spectrometry, and confocal imaging. Effects of periaxin deficiency on the stability of lens fiber cell AJs were evaluated using perixin-null mice. Results: alphaN-catenin exhibits discrete distribution to lens fibers in both mouse and human lenses, undergoing a robust up-regulation during fiber cell differentiation and maturation. Epithelial-specific alpha-catenin (alphaE-catenin), in contrast, distributes primarily to the lens epithelium. alphaN-catenin and N-cadherin reciprocally coimmunoprecipitate and colocalize along with beta-catenin, actin, spectrin, vinculin, Armadillo repeat protein deleted in velo-cardio-facial syndrome homolog, periaxin, and ankyrin-B in lens fibers. Fiber cells from periaxin-null mouse lenses revealed disrupted N-cadherin/alphaN-catenin-based AJs. Conclusions: These results suggest that the discrete shift in alpha-catenin expression from alphaE-catenin to alphaN-catenin subtype that occurs during lens epithelial cell differentiation may play a key role in fiber cell cytoarchitecture by regulating the assembly and stability of N-cadherin-based AJs. This study also provides evidence for the importance of the fiber cell-specific cytoskeletal interacting periaxin, in the stability of N-cadherin/alphaN-catenin-based AJs in lens fibers. |