Identification of a novel intermediate filament-linked N-cadherin/gamma-catenin complex involved in the establishment of the cytoarchitecture of differentiated lens fiber cells.
Tissue morphogenesis and maintenance of complex tissue architecture requires a variety of cell-cell junctions. Typically, cells adhere to one another through cadherin junctions, both adherens and desmosomal junctions, strengthened by association with cytoskeletal networks during development. Both beta- and gamma-catenins are reported to link classical cadherins to the actin cytoskeleton, but only gamma-catenin binds to the desmosomal cadherins, which links them to intermediate filaments through its association with desmoplakin. Here we provide the first biochemical evidence that, in vivo, gamma-catenin also mediates interactions between classical cadherins and the intermediate filament cytoskeleton, linked through desmoplakin. In the developing lens, which has no desmosomes, we discovered that vimentin became linked to N-cadherin complexes in a differentiation-state specific manner. This newly identified junctional complex was tissue specific but not unique to the lens. To determine whether in this junction N-cadherin was linked to vimentin through gamma-catenin or beta-catenin we developed an innovative "double" immunoprecipitation technique. This approach made possible, for the first time, the separation of N-cadherin/gamma-catenin from N-cadherin/beta-catenin complexes and the identification of multiple members of each of these isolated protein complexes. The study revealed that vimentin was associated exclusively with N-cadherin/gamma-catenin junctions. Assembly of this novel class of cadherin junctions was coincident with establishment of the unique cytoarchitecture of lens fiber cells. In addition, gamma-catenin had a distinctive localization to the vertices of these hexagonally shaped differentiating lens fiber cells, a region devoid of actin; while beta-catenin co-localized with actin at lateral cell interfaces. We believe this novel vimentin-linked N-cadherin/gamma-catenin junction provides the tensile strength necessary to establish and maintain structural integrity in tissues that lack desmosomes.
Leonard
Michelle
M
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 571 Jefferson Alumni Hall, 1020 Locust Street, Philadelphia, PA 19107, USA.
Chan
Yim
Y
Menko
A Sue
AS
D000199:Actins / Q000032:analysis / Q000502:physiology; D000818:Animals; D015820:Cadherins / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002642:Chick Embryo; D004847:Epithelial Cells / Q000166:cytology; D005455:Fluorescent Antibody Technique; D007381:Intermediate Filament Proteins / Q000502:physiology*; D007908:Lens, Crystalline / Q000166:cytology* / Q000196:embryology*; D014746:Vimentin / Q000502:physiology; D051185:gamma Catenin / Q000502:physiology*
D000199:Actins; D015820:Cadherins; D007381:Intermediate Filament Proteins; D014746:Vimentin; D051185:gamma Catenin