THE LIFE-CYCLE OF A CONNEXIN - GAP JUNCTION FORMATION, REMOVAL, AND DEGRADATION

Gap junction proteins, connexins, possess many properties that are aty pical of other well-characterized integral membrane proteins. Oligomer ization of connexins into hemichannels (connexons) has been shown to o ccur after the protein exits the endoplasmic reticulum. Once delivered to the cell surface, connexons from one cell pair with connexons from a neighboring cell, a process that is facilitated by calcium-dependen t cell adhesion molecules. Channels cluster into defined plasma membra ne domains to form plaques. Unexpectedly, gap junctions are not stable (half-life <5 h) and are thought to be retrieved back into the cell i n the form of double membrane structures when one cell internalizes th e entire gap junction through endocytosis. Evidence exists for both pr oteasomal and lysosomal degradation of gap junctions, and it remains p ossible that both mechanisms are involved in connexin degradation. In addition to opening and closing of gap junction channels (gating), the formation and removal of gap junctions play an essential role in regu lating the level of intercellular communication.