Biosynthesis and structural composition of gap junction intercellular membrane channels.
Gap junction channels assemble as dodecameric complexes, in which a hexameric connexon (hemichannel) in one plasma membrane docks end-to-end with a connexon in the membrane of a closely apposed cell to provide direct cell-to-cell communication. Synthesis, assembly, and trafficking of the gap junction channel subunit proteins referred to as connexins, largely appear to follow the general secretory pathway for membrane proteins. The connexin subunits can assemble into homo-, as well as distinct hetero-oligomeric connexons. Assembly appears to be based on specific signals located within the connexin polypeptides. Plaque formation by the clustering of gap junction channels in the plane of the membrane, as well as channel degradation are poorly understood processes that are topics of current research. Recently, we tagged connexins with the autofluorescent reporter green fluorescent protein (GFP), and its cyan (CFP), and yellow (YFP) color variants and combined this reporter technology with single, and dual-color, high resolution deconvolution microscopy, computational volume rendering, and time-lapse microscopy to examine the detailed organization, structural composition, and dynamics of gap junctions in live cells. This technology provided for the first time a realistic, three-dimensional impression of gap junctions as they appear in the plasma membranes of adjoining cells, and revealed an excitingly detailed structural organization of gap junctions never seen before in live cells. Here, I summarize recent progress in areas encompassing the synthesis, assembly and structural composition of gap junctions with a special emphasis on the recent results we obtained using cell-free translation/ membrane-protein translocation, and autofluorescent reporters in combination with live-cell deconvolution microscopy.
Falk
M M
MM
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. mfalk@scripps.edu
D000818:Animals; D017630:Connexins / Q000096:biosynthesis* / Q000737:chemistry / Q000648:ultrastructure; D006801:Humans; D007473:Ion Channels / Q000096:biosynthesis* / Q000737:chemistry* / Q000648:ultrastructure; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry; D021381:Protein Transport / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D017630:Connexins; D007473:Ion Channels; D020033:Protein Isoforms