Different consequences of @entity231 -associated mutations at adjacent positions in the first extracellular boundary of XXXX .

@entity1 @entity1522 @entity1238 @entity231 @entity72544 @entity11305 @entity44443 @entity460
Gap junction channels, which are made of connexins, are critical for intercellular communication, a function that may be disrupted in a variety of diseases. We studied the consequences of two @entity231 -associated mutations at adjacent positions at the first extracellular boundary in @entity1 @entity11305 ( @entity11305 ), @entity72544 and @entity44443 . Both of these mutants formed gap junctional plaques when they were expressed in HeLa cells, suggesting that they trafficked to the plasma membrane properly. However, their functional properties differed. Dual two-microelectrode voltage-clamp studies showed that @entity72544 did not form functional intercellular channels in paired @entity1238 oocytes or hemichannel currents in single oocytes. When @entity72544 was coexpressed with wild-type @entity11305 , the mutant acted as a dominant negative inhibitor of wild-type function. In contrast, @entity44443 formed both functional gap junctional channels and hemichannels. @entity44443 exhibited greatly enhanced currents compared with wild-type @entity11305 in the presence of physiological @entity460 concentrations. This increase in hemichannel activity persisted when @entity44443 was coexpressed with wild-type lens connexins, consistent with a dominant gain of hemichannel function for @entity44443 . These data suggest that although these two mutations are in adjacent @entity1522 , they have very different effects on connexin function and cause disease by different mechanisms: @entity72544 inhibits gap junctional channel function; @entity44443 reduces cell viability by forming open hemichannels.
