Poster abstracts
Poster number 1 submitted by Marissa Boyer
Elucidating the functions and mechanisms of disease-related adhesion proteins, cadherin-23 and calsyntenins 1-3
Marissa Boyer (Department of Chemistry and Biochemistry, The Ohio State University), Pedro de la Torre (Department of Chemistry and Biochemistry, The Ohio State University), Yoshie Narui (Center for Electron Microscopy and Analysis, The Ohio State University), Marcos Sotomayor (Department of Chemistry and Biochemistry, The Ohio State University)
Abstract:
Adhesion proteins are keystones to the proper function of cells throughout the body and mutations present within these proteins can lead to various disorders, including deafness and Alzheimer’s disease. Of particular importance to these conditions are members of the cadherin superfamily of proteins, cadherin-23 and calsyntenins (1, 2, and 3), which are thought to mediate calcium-dependent adhesion and signaling. Cadherin-23, featuring an enormous dimeric extracellular domain with 27 extracellular cadherin repeats, is found in the inner ear and is essential for sound perception. How cadherin-23 forms parallel dimers is unknown. The smaller and less well-characterized calsyntenins have two extracellular cadherin-like repeats and a cytoplasmic domain that binds calcium. They are found in brain synapses and axonal trafficking organelles, yet their exact role in adhesion and signaling is unclear. To understand the molecular basis of cadherin-23 dimerization and the function of calsyntenins we have cloned, expressed, purified and refolded various fragments of these proteins for biochemical and structural characterization. Our preliminary results from size exclusion chromatography experiments suggest that cadherin-23 extracellular repeats 25-26 can facilitate parallel dimerization, with implications for the mechanisms underlying sound perception and hereditary deafness. In contrast, experiments on refolded putative calsyntenin cadherin repeats are less conclusive about their oligomerization state and adhesive function. Additional experiments aimed at elucidating the calsyntenins’ varying functions within neural synapses are ongoing.
Keywords: adhesion, structure