First published online August 24, 2006
Journal of Cell Science 119, 1702e (2006)
© The Company of Biologists Limited
Nedd4 plugs the gap
The gap junctions that connect neighbouring cells continually turn over, allowing tight regulation of intercellular communication. Proteasomes and/or lysosomes are thought to degrade the connexin proteins that make up these junctions, but how this is regulated has been unclear. Angel Alonso and co-workers now reveal that a ubiquitin ligase, Nedd4, is the key (see p. 3634). Like other ubiquitin ligases, Nedd4 promotes attachment of ubiquitin to its substrates, which marks them for degradation by the proteasome. Alonso and co-workers show that the most common connexin, Cx43, interacts with Nedd4 in vitro and define the regions of the proteins responsible - the interaction involves the C-terminus of Cx43 and all three WW domains of Nedd4. The authors then use coimmunoprecipitation and immunofluorescence analyses to demonstrate that Nedd4 and Cx43 interact in vivo. Critically, they also show that knocking down Nedd4 expression by RNAi leads to accumulation of excessive numbers of Cx43-containing gap junctions at the plasma membrane. Nedd4 therefore appears to play a pivotal role controlling the abundance of gap junctions in cells.
Related articles in JCS:
- Ubiquitin protein ligase Nedd4 binds to connexin43 by a phosphorylation-modulated process
- Kerstin Leykauf, Mojibrahman Salek, Jörg Bomke, Matthias Frech, Wolf-Dieter Lehmann, Matthias Dürst, and Angel Alonso
JCS 2006 119: 3634-3642.
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