Connexins assembly

Gap junctions are the sites of intercellular membrane channels which provide for direct cytoplasmic continuity between the adjacent cells (Simon and Goodenough, 1998). A wealth of recent data have indicated that connexins are the proteins assembled into gap junction channels, and represent the building blocks of these channels (see the reviews of Bennett, 1997 Hormuzdi et al., 2004). 

J.K.. VanSlyke, LS. Musil, Analysis of connexin intracellular transport and assembly, Methods 20, 156-164(2000). 

A.F. Paulson, P.D. Lampe, R.A. Meyer, E. TenBroek, M.M. Atkinson, T.F. Walseth, R.G. Johnson, Cyclic AMP and LDL trigger a rapid enhancement in gap junction assembly through a stimulation of connexin trafficking, J Cell Science 113,3037-3049 (2000). 

CD. Cooper, P.D. Lampe, Casein kinase 1 regulates connexin-43 gap junction assembly, J Biol Chem 277,4962-44968(2003). 

Connexin protein is unique in forming a gated pore through two membranes. Two questions particular to this structure are (1) how is the junctional channel assembled (e.g., how do the two hemichannels find each other and interact to form a stable structure) and (2) what is the interaction between... 

It is hoped that such studies of single hemichannels will be complemented by studies of reconstituted junctional channels the double-membrane form. Development of a stable, well-characterized, and well-controlled double-membrane system is a challenging prospect. The literature on osmotic control of fusion of apposed bulged bilayers may be helpful in this regard (120, 121). Such a system would permit exploration of the forces involved in the assembly of junctional channels, which would be of interest from biophysical and cellular perspectives. For example, does the space between two membranes need to be dehydrated for hemichannels to interact (122) Do the hemichannels find each other by random interactions or does dielectric attraction (123-125) play a role Once junctional channels are formed, how reversible is the interaction between them and what forces tend to stabilize it Most important, how are the permeability, gating, and modulation of single hemichannels altered by interactions with each other in the doublemembrane form These and other considerations make the exploration of connexin channels in reconstituted systems of profound interest and promising prospects. 

---