Homophilic and Heterophilic Interactions of Type II Cadherins Identify Specificity Groups Underlying Cell-Adhesive Behavior
| Autor: | Indrajyoti Indra, Anna Kaczynska, Julia Brasch, Phinikoula S. Katsamba, Lawrence Shapiro, Benjamin Kaeser, Goran Ahlsen, Barry Honig, O.J. Harrison, Regina B. Troyanovsky, Sergey M. Troyanovsky |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell DNA Mutational Analysis Neuronal targeting Molecular binding General Biochemistry Genetics and Molecular Biology Article Cell Line 03 medical and health sciences Mice medicine Cell Adhesion Animals Humans Amino Acid Sequence Cell adhesion lcsh:QH301-705.5 Conserved Sequence Phylogeny Cadherin Chemistry Cadherins Cell biology 030104 developmental biology medicine.anatomical_structure Targeted Mutation lcsh:Biology (General) Mutation Protein Multimerization Protein Binding |
| Zdroj: | Cell reports Cell Reports, Vol 23, Iss 6, Pp 1840-1852 (2018) |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY Type II cadherins are cell-cell adhesion proteins critical for tissue patterning and neuronal targeting but whose molecular binding code remains poorly understood. Here, we delineate binding preferences for type II cadherin cell-adhesive regions, revealing extensive heterophilic interactions between specific pairs, in addition to homophilic interactions. Three distinct specificity groups emerge from our analysis with members that share highly similar heterophilic binding patterns and favor binding to one another. Structures of adhesive fragments from each specificity group confirm near-identical dimer topology conserved throughout the family, allowing interface residues whose conservation corresponds to specificity preferences to be identified. We show that targeted mutation of these residues converts binding preferences between specificity groups in biophysical and co-culture assays. Our results provide a detailed understanding of the type II cadherin interaction map and a basis for defining their role in tissue patterning and for the emerging importance of their heterophilic interactions in neural connectivity. In Brief Type II cadherins are a family of vertebrate cell adhesion proteins expressed primarily in the CNS. Brasch et al. measure binding between adhesive fragments, revealing homophilic and extensive selective heterophilic binding with specificities that define groups of similar cadherins. Structures reveal common adhesive dimers, with residues governing cell-adhesive specificity. |
| Databáze: | OpenAIRE |
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