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.
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 571 Jefferson Alumni Hall, 1020 Locust Street, Philadelphia, PA 19107, USA.
Michelle
M
Leonard
Yim
Y
Chan
A Sue
AS
Menko
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