Untangling Desmosomal Knots with Electron Tomography

Cell adhesion by adherens junctions and desmosomes relies on interactions between cadherin molecules. However, the molecular interfaces that define molecular specificity and that mediate adhesion remain controversial. We used electron tomography of plastic sections from neonatal mouse skin to visualize the organization of desmosomes in situ. The resulting three-dimensional maps reveal individual cadherin molecules forming discrete groups and interacting through their tips. Fitting of an x-ray crystal structure for C-cadherin to these maps is consistent with a flexible intermolecular interface mediated by an exchange of amino-terminal tryptophans. This flexibility suggests a novel mechanism for generating both cis and trans interactions and for propagating these adhesive interactions along the junction.

[1]  K. McDonald,et al.  High-pressure freezing for preservation of high resolution fine structure and antigenicity for immunolabeling. , 1999, Methods in molecular biology.

[2]  Carien M. Niessen,et al.  The Juxtamembrane Region of the Cadherin Cytoplasmic Tail Supports Lateral Clustering, Adhesive Strengthening, and Interaction with p120ctn , 1998, The Journal of cell biology.

[3]  J. Engel,et al.  Homophilic adhesion of E‐cadherin occurs by a co‐operative two‐step interaction of N‐terminal domains. , 1996, The EMBO journal.

[4]  Peter D. Kwong,et al.  Structural basis of cell-cell adhesion by cadherins , 1995, Nature.

[5]  Wayne A. Hendrickson,et al.  Structure-Function Analysis of Cell Adhesion by Neural (N-) Cadherin , 1998, Neuron.

[6]  M. Amagai,et al.  Autoantibodies against the amino-terminal cadherin-like binding domain of pemphigus vulgaris antigen are pathogenic. , 1992, The Journal of clinical investigation.

[7]  J. Hill,et al.  Desmocollins form a distinct subset of the cadherin family of cell adhesion molecules. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[8]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[9]  Clara Franzini-Armstrong,et al.  Tomographic 3D Reconstruction of Quick-Frozen, Ca2+-Activated Contracting Insect Flight Muscle , 1999, Cell.

[10]  M. Takeichi,et al.  Functional correlation between cell adhesive properties and some cell surface proteins , 1977, The Journal of cell biology.

[11]  D. DeRosier,et al.  Actin in the inner ear: the remarkable structure of the stereocilium , 1980, Nature.

[12]  B. Geiger,et al.  The molecular basis for the assembly and modulation of adherens-type junctions. , 1990, Cell differentiation and development : the official journal of the International Society of Developmental Biologists.

[13]  R. Kemler,et al.  The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. , 1989, The EMBO journal.

[14]  J. Engel,et al.  Single amino acid substitutions in one Ca2+ binding site of uvomorulin abolish the adhesive function , 1990, Cell.

[15]  B. Angst,et al.  COMMENTARY The cadherin superfamily: diversity in form and function , 2022 .

[16]  W J Nelson,et al.  Mechanism for transition from initial to stable cell-cell adhesion: kinetic analysis of E-cadherin-mediated adhesion using a quantitative adhesion assay , 1996, The Journal of cell biology.

[17]  J. Stanley,et al.  Intracellular domain of desmoglein 3 (pemphigus vulgaris antigen) confers adhesive function on the extracellular domain of E-cadherin without binding catenins , 1995, The Journal of cell biology.

[18]  O. Pertz,et al.  A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular details of E‐cadherin homoassociation , 1999, The EMBO journal.

[19]  K. Herrenknecht,et al.  A possible new adhesive site in the cell-adhesion molecule uvomorulin , 1990, Mechanisms of Development.

[20]  I. Rayment,et al.  Three-dimensional structure of myosin subfragment-1 from electron microscopy of sectioned crystals , 1991, The Journal of cell biology.

[21]  Wolfgang Baumeister,et al.  Electron tomography: towards visualizing the molecular organization of the cytoplasm. , 2002, Current opinion in structural biology.

[22]  B. Gumbiner,et al.  Cell Adhesion: The Molecular Basis of Tissue Architecture and Morphogenesis , 1996, Cell.

[23]  D. Garrod,et al.  Desmosomal adhesion inhibits invasive behavior. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[24]  J. Holton,et al.  Cloning and sequence analysis of desmosomal glycoproteins 2 and 3 (desmocollins): cadherin-like desmosomal adhesion molecules with heterogeneous cytoplasmic domains , 1991, The Journal of cell biology.

[25]  R. Kemler,et al.  The Membrane-proximal Region of the E-Cadherin Cytoplasmic Domain Prevents Dimerization and Negatively Regulates Adhesion Activity , 1998, The Journal of cell biology.

[26]  T. Boggon,et al.  C-Cadherin Ectodomain Structure and Implications for Cell Adhesion Mechanisms , 2002, Science.

[27]  Akinao Nose,et al.  Localization of specificity determining sites in cadherin cell adhesion molecules , 1990, Cell.

[28]  W. Hendrickson,et al.  Considerations on the folding topology and evolutionary origin of cadherin domains. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[29]  M Marko,et al.  The Emergence of Electron Tomography as an Important Tool for Investigating Cellular Ultrastructure , 2001, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[30]  C. Kay,et al.  Multiple cadherin extracellular repeats mediate homophilic binding and adhesion , 2001, The Journal of cell biology.

[31]  F. van Roy,et al.  Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. , 2000, Journal of molecular biology.

[32]  O. Blaschuk,et al.  Identification of a cadherin cell adhesion recognition sequence. , 1990, Developmental biology.

[33]  S. J. Smith,et al.  Quantitative analysis of cadherin-catenin-actin reorganization during development of cell-cell adhesion , 1996, The Journal of cell biology.

[34]  W. Birchmeier,et al.  Epithelial-mesenchymal transitions in cancer progression. , 1996, Acta anatomica.

[35]  Minh N. H. Nguyen,et al.  Wild-Type Nonneuronal Cells Extend Survival of SOD1 Mutant Motor Neurons in ALS Mice , 2003, Science.

[36]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[37]  D. Langosch,et al.  Mutations affecting transmembrane segment interactions impair adhesiveness of E-cadherin. , 1999, Journal of cell science.

[38]  D. Leckband,et al.  Direct measurements of multiple adhesive alignments and unbinding trajectories between cadherin extracellular domains. , 2001, Biophysical journal.

[39]  J R Kremer,et al.  Computer visualization of three-dimensional image data using IMOD. , 1996, Journal of structural biology.

[40]  G. Wagner,et al.  E-cadherin: a distant member of the immunoglobulin superfamily , 1995, Science.

[41]  M. Ikura,et al.  Solution structure of the epithelial cadherin domain responsible for selective cell adhesion , 1995, Science.

[42]  A. Klug,et al.  Physical principles in the construction of regular viruses. , 1962, Cold Spring Harbor symposia on quantitative biology.

[43]  D. Vestweber,et al.  Identification of a putative cell adhesion domain of uvomorulin. , 1985, The EMBO journal.

[44]  Elaine Fuchs,et al.  Directed Actin Polymerization Is the Driving Force for Epithelial Cell–Cell Adhesion , 2000, Cell.

[45]  W. Baumeister,et al.  Macromolecular Architecture in Eukaryotic Cells Visualized by Cryoelectron Tomography , 2002, Science.

[46]  M. Ikura,et al.  Structural basis of calcium-induced E-cadherin rigidification and dimerization , 1996, Nature.