ABSTRACT
Gap junctional intercellular communication is established when connexin proteins oligomerize into connexon hemichannels, which then pair at the cell surface with connexons from neighboring cells to form functional gap junction channels. Gap junction channels routinely cluster into gap junction plaques, which can exhibit dynamic characteristics while under the frequent processes of formation and removal from the cell surface. We have three lines of evidence to suggest that one mechanism of gap junction removal occurs when one of two contacting cells internalizes the gap junction contribution from both cells. First, in coculture experiments, green fluorescent protein-tagged connexin43 (Cx43-GFP) expressed in normal rat kidney (NRK) cells can be internalized into contacting cells that do not express Cx43-GFP, and the incidences of identifying these internalized structures increase in the presence of lysosomal inhibitors. Secondly, time-lapse imaging of live NRK cells revealed that large areas of gap junction plaques containing Cx43-GFP were internalized as vesicular-like structures into one of two adjacent cells. Finally, when live NRK cells that express endogenous Cx43 were microinjected with anti-Cx43 antibodies, antibody-tagged gap junctions were visualized in cells that contacted the microinjected cell within 3-6.5 hours. Together our results strongly suggest that one mechanism of gap junction removal from the cell surface involves a unique process in which the entire gap junction or a fragment of it is internalized into one of the two contacting cells as an annular junction.
Subject(s)
Gap Junctions/metabolism , Animals , Biological Transport , Cell Line , Connexin 43/metabolism , Epithelial Cells/metabolism , Green Fluorescent Proteins , Iris/cytology , Iris/metabolism , Luminescent Proteins/metabolism , Microscopy, Immunoelectron , Rats , Recombinant Fusion Proteins/metabolismABSTRACT
Effort thrombosis usually afflicts an extremity and is caused by compression. This case report, in contrast, involves superior mesenteric and left portal vein septic thrombosis in a backpacker following prolonged hiking and abdominal straining. The condition may have been caused by localized splanchnic venous ischemia, erosion of the bowel-blood barrier, and release of bacterial endotoxin in this dehydrated and detrained athlete. Diagnosis of this disorder is aided by noting characteristic abdominal pain, fever, nausea, and vomiting, as well as by imaging with MRI, CT, or duplex ultrasonography. Antibiotics and anticoagulants are key to treatment.