Molecular Biological and Biophysical Structure-Function Analyses of Connexin46

..................................................................................................................................... 1 Zusammenfassung ...................................................................................................................... 3 Chapter 1. General Introduction ............................................................................................ 6 1.1 Gap junctions and connexins ....................................................................................... 7 1.2 The physical structure of gap junction channels ....................................................... 10 1.3 Expression and degradation of gap junction channels ............................................... 13 1.4 Regulation of gap junction dependent cell-to-cell communication ........................... 18 1.5 Lens gap junction connexins ..................................................................................... 21 1.6 Aim of the thesis ........................................................................................................ 23 1.7 References ................................................................................................................. 25 Chapter 2. The Role of the C-Terminus in Functional Expression and Internalization of Rat Connexin46 (rCx46) .......................................................................................................... 36 Chapter 3. Cataract-associated D3Y mutation of human connexin46 (hCx46) increases the dye coupling of gap junction channels and suppresses the voltage sensitivity of hemichannels ............................................................................................................................ 38 Chapter 4. Discussion .......................................................................................................... 40 4.1 The CT of rCx46 is involved in functional expression ............................................. 40 4.2 The CT is involved in removal of rCx46 gap junction channels from cell surface ... 43 4.3 The role of the CT in regulation of gap junction plaque formation in the lens ......... 45 4.4 The D3Y mutation in hCx46 did not affect trafficking of gap junction channels but alters dye permeability ................................................................................................... 46