First published online February 22, 2006
Journal of Cell Science 119, 502e (2006)
© The Company of Biologists Limited
Elmo's fire blocks Dock180 destruction
The proteins Dock180 and Elmo1 have important roles in signalling, cytoskeletal regulation and phagocytosis. They are proposed to function together as an unconventional, `bipartite' GEF (guanine nucleotide exchange factor) that controls the activity of the GTPase Rac. Shinya Tanaka and co-workers now reveal that Dock180 depends on Elmo1 not only for GEF activity but also to escape destruction (see p. 923). They observe that increasing the levels of Elmo1 stabilises overexpressed Dock180, which is significantly degraded over a 24 hour period. The authors then show that Dock180 is ubiquitylated at the plasma membrane in vivo and that its levels can be stabilised by inhibitors of the proteasome. They go on to use deletion mutants to demonstrate that binding of Elmo1 to Dock180 specifically inhibits its ubiquitylation and consequent degradation. Finally, Tanaka and co-workers show that upstream signalling promotes membrane translocation and ubiquitylation of DOCK180. They propose that that Elmo1 is important for correct spatiotemporal regulation of Dock180 and speculate that ubiquitin-dependent degradation of Dock180 could allow localised activation of Rac at the plasma membrane.
Related articles in JCS:
- Elmo1 inhibits ubiquitylation of Dock180
- Yoshinori Makino, Masumi Tsuda, Shin Ichihara, Takuya Watanabe, Mieko Sakai, Hirofumi Sawa, Kazuo Nagashima, Shigetsugu Hatakeyama, and Shinya Tanaka
JCS 2006 119: 923-932.
[Abstract]
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