The Gap Junction Communication Channel

Communication plays an important role in the rapid Connexin Structure progress of modern society. We live in an age when Gap junctions exhibit a hierarchy of assembly. The prininformation is transmitted through many different pathcipal structural component, the membrane protein conways and in many different forms to influence our daily nexin, is organized into the basic unit of structure, the decisions. However, although we live in communities, connexon, which is a hexameric structure with a toroid we still treasure our individuality. By analogy, the surappearance in negative-stained preparations. The famvival of multicellular organisms depends on each cell ily of connexin proteins includes at least 12 members in type retaining its individuality, even though all cellular rodents (Table 1; Kumar and Gilula, 1992). An individual activities must be coordinated with other cells. Organconnexon from one cell docks or associates with a corisms have evolved multiple strategies to achieve this responding connexon on a neighboring cell to form a goal, which include long-range interactions mediated gap junction channel, and multiple channels, in turn, by neural or endocrine mechanismsor short-range intercluster or aggregate in the plane of the membrane to actions that include direct physical or cell–cell contact. form gap junction plaques. The properties of the gap While the first strategy involves interactions at a disjunction channels are defined by the connexins. Structance, one mode of direct communication involves the tural and biophysical studies are being used to define cell-to-cell transmission of molecules through channels the mechanism by which connexins function. in a specialized cell surface membrane structure, the Connexins are the principal protein component of gap gap junction. junctions. There is much evidence to support the fact Gap junctions contain channels that connect neighthat the connexins alone (assembled in a lipid bilayer) boring cells. They differ from other membrane channels are responsible for the generation of gap junctional since they exist between two cells, they are relatively channels. This evidence includes the following: connonspecific, and the molecular movement through the nexin sequences are consistent with an integral memchannels occurs by passive diffusion. The gap junctional brane protein that has a transmembrane domain conchannels have an apparent selectivity based principally taining polar amino acids that would contribute to the on molecular size, allowing the movement of molecules formation of a channel lining; reconstitution of purified smaller than 1000 Da, such as cAMP, but preventing connexins into artificial membranes yields functional the movement of proteins or nucleic acids. Small inforchannels (reviewed by Buehler et al., 1995); expression mational molecules, such as certain morphogens, could of connexin cDNAs in heterologous systems (including be directly transmitted between cells via gap junctions. yeast) yields not only functional gap junction channels, Consequently, this type of communication is an imporbut also gap junctions that are ultrastructurally identical tant mechanism for regulating events between cells durto those occurring naturally invivo; electron microscopic ing embryogenesis (Warner et al., 1984) and during the immunocytochemical studies localize connexins to gap normal function of organs, such as the heart. junction plaques; and the distribution of connexins obApart from a few terminally differentiated cells, such served in vivo can be related to gap junctional communias skeletal muscle, erythrocytes, and circulating lymcation pathways. phocytes,most cells innormal tissues generally commuEach of the connexins appears to fit the general toponicate via gap junctions. These junctions exist in almost logical model for gap junction protein (Figure 1). In this all animals, both vertebrates and invertebrates, and model, the polypeptide traverses the lipid bilayer four higher plant cells utilize a similar mechanism for cell–cell times, with both the Nand C-termini facing the cytocommunication via the plasmodesmata structures. plasm (Milks et al., 1988; cf. Yeager and Gilula, 1992). There has been rapid progress recently in identifying Analysis of the different connexins indicates that one of and characterizing a multigene family that codes the