Role of E-cadherin’s N-glycans in tissue morphogenesis

• Applicant: Professor Dr. Jörg Großhans
• Subject Area: Developmental Biology ; Cell Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 525776139

The evolutionary conserved E-cadherin (shotgun in Drosophila) is the prototype of a cell adhesion molecule in epithelia, which on the one side is responsible for homotypic and Calcium dependent cell-cell adhesion and on the other is connected to the cortical actomyosin cytoskeleton by forming a trimeric complex with beta-catenin (armadillo in Drosophila) and alpha-catenin. Beside such generic trimeric complexes, E-cadherin is found in super-molecular complexes of several hundred molecule, which may or may not be engaged in adhesion and trimeric complexes. Being centrally positioned at the force transmission between epithelial cells, E-cadherin plays a pivotal role in mechanical cell communication. The molecular mechanism of mechanotransduction has been difficult to investigate given the intertwined E-cadherin functions in adhesion, cortical link and mechanotransduction. Based on findings that hypo-N-glycosylated E-cadherin is impaired in clustering, cortical interactions and certain aspects of cell-cell communication, we propose to systematically investigate the contributions of N-glycans to the functions of E-cadherin in a physiological setting during tissue morphogenesis in Drosophila embryos by a series of E-cadherin mutations at N-glycosylation sites. The phenotype of these mutations will be investigated by established molecular and functional assays for E-cadherin mobility, complex formation, mechanics of junctions, adhesion, cell signalling. The phenotypes in nano-structure will be investigated by high resolution microscopy and DNA-paint single molecular localization.

• DFG Programme: Research Grants