STRUCTURE AND FUNCTION OF GAP JUNCTION CO MMUNICATION

Cell-to-cell communication through gap junctions (GJ) represents a dir ect route of exchange of informations between neighboring cells within tissues and organs. GJ are formed from the assembly of a large number of channels that differ from the other known channels because they co nnect the cytoplasm of adjacent cells. The GJ channel is built from tw o parts I the connexons. A connexon inserted into the plasma membrane of a cell interacts with another connexon belonging to an adjacent cel l. Connexons are composed of proteins proteins with four transmembrane domains that are named connexins (Cx). Six Cx form a connexon. Cx bel ong to a protein family with 13 know members at present. Each Cx is de fined by its molecular mass in kDa (ex : Cx32, Cx43...). A given cell type expresses one or several Cx. The cell to cell transfer of molecul es through GJ channels exhibit a size selectivity; only molecules with a molecular mass lower than 1 000 Da such as ions and second messenge rs freely pass through GJ. Depending on the Cx they are made of GJ see m to differ somewhat in their permeability properties. Cell-to-cell co mmunication via GJ is a regulated process. GJ channels carl be either open or closed. GJ mediated cell-to-cell communication or junctional c oupling can be detected and quantified by visualization of the cell to cell transfer of a fluorescent probe (such as Lucifer Yellow...) prev iously introduced in a single cell by microinjection. The presence of GJ channels can also be identified by recording the passage of an elec tric current between contiguous cells. GJ are involved in numerous fun damental biological processes from the embryonic development to the ho meostasis in adult tissues and organs. GJ coordinate cell activities a nd sometimes synchronize cell behaviour. This is the case for the prop agation of the excitation wave in the cardiac muscle and smooth muscle . GJ mediate metabolic cooperation between cells; they represent a way of supply of nutrients for tissues that are weakly or not vascularize d. GJ take part iii the control of cell proliferation. The loss of GJ- mediated cell-to-cell communication is a common feature of transformed cells and the re-establishment of junctional coupling is associated w ith a decrease of tumoregenicity. Allowing rite cell-to-cell transfer of second messengers, GJ participate (and sometimes control the respon se of a cell population to signalling molecules. It is known for examp le that hormones influence the expression of Cx and thus the level of the junctional coupling and that communication via GJ has an effect on the type and extent of action of hormones.