Innexin Gap Junctions

The Innexin lifecycle

Diagram showing potential lifecycle pathway for Innexin molecules in a cell

Figure legend: The innexin lifecyle. There are three consistently distinguishable innexin-immunopositive subcellular domains within salivary gland cells: A/ small vesicles near the nucleus (Image: Nucleus-associated vesicles), B/ plaques (Image: Inx2 plaques), C/ a mixture of large and small vesicles near the basal pole (Image: Annular junctions). The diagram above shows two representative cells each indicating a hypothetical pathway leading from innexin synthesis to incorporation into plaques to degradation - the 'standard' innexin lifecycle (...'standard' because it only considers the classical role of gap junctions at the plasma membrane and completely ignores the recent discovery of innexins in the nucleus (Ostrowski et al, 2008, inx7 Summary) defense, not much is known about the nuclear role of innexins or how they get there). Pathway 1 A→B→C proposes that innexins are incorporated into membrane and packaged for transport in the small vesicles (A) near the cell nucleus. These vesicles are then transported to the lateral plasma membrane for integration into plaques (B). Older channels are internalised from the basal region of the lateral membrane as annular junctions (C). Pathway 2 A→C→B proposes again that channel synthesis and transport is mediated by the small vesicles (A). These are then transported to a sorting region near the basal (salivary gland outer surface) surface of cells (C). Incorporation of newly synthesized channels into plaques (B) and removal of older channels is proposed to be regulated at the basal end of cells by machinery in the sorting region (C).

Whether either of the hypothetical lifecycle pathways described above turn out to be correct for salivary gland cells, and are generalisable to other cell-types, remains to be seen. These lifecycle pathways are based on observations of fixed tissue, antibody-stained movement tracking was possible. There is some visual evidence that small, innexin-immunopositive vesicles (putative transport vesicles) are present at both the basal and apical ends of the region of lateral cell membrane that is occupied by gap junctions. At the basal end, small and large vesicles are observed - potentially a mix of transport and endocytic vesicles. At the apical end, only small (...transport?) vesicles are observed. Hopefully, at some stage a Drosophila lab will attempt real-time imaging to elucidate the true pathway in salivary glands or some other amenable tissue. A number of approaches are available to achieve this including; GFP-tagged innexin constructs (....such as that referred to in Lehmann et al. 2006) or tetracysteine-tagging of innexins (Gaietta et al. 2002...reference for tetracys-tagged connexins). The notion that the basal region of salivary gland cells may act as a sorting zone (similar to the sub-apical sorting zone described in some vertebrate cells (Van Ijzendoorn and Hoekstra 1999) is based on a few observations:

  1. - The vesicles observed at the basal pole of salivary gland cells range in size from small (possibly transport vesicles) to large (possibly annular junctions).
  2. - Small putative transport vesicles are mainly detected around the cell nucleus and in areas basal to the nucleus. However, no small vesicles have been observed in the cytoplasm between the nucleus and the lateral plasma membrane (at least in pupal glands). It's possible that our sampled cells did not include a time window where vesicle transport is maximal and more likely to be detected.
  3. - The basal region of the salivary gland cells is rich in actin filaments that could provide the infrastructure required for a sorting zone (Images: Inx2 and F-actin association and Linear arrangement of Inx2 on the cell surface).
  4. - Still images of the baso-lateral junction region of pupal salivary gland cells just 'looks' like it's a zone undergoing a lot of activity....the most intense innexin-staining is detected in, and around, this area.

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