First published online June 28, 2004
Journal of Cell Science 117, 1502e (2004)
© The Company of Biologists Limited
Traffic diverted by RhoB
Rho GTPases have well-established roles in cytoskeletal reorganization but are also increasingly being implicated in membrane trafficking. RhoB, for example, is present on endocytic vesicles, where it seems to regulate trafficking of epidermal growth factor receptors (EGF-Rs). Like other small GTPases, RhoB has an isoprenoid anchor at its C-terminus. Uniquely, this can be either a farnesyl group (like Ras) or a geranylgeranyl group (like other Rho proteins). On p. 3221, Harry Mellor and co-workers show that the distinction is important for EGF-R trafficking. They find that geranylgeranylated RhoB (RhoB-GG) resides in endocytic compartments but farnesylated RhoB (RhoB-F) is at the plasma membrane. They also find that treatment with farnesyl transferase inhibitors (FTIs), which tips the balance in favour of Rho-GG generation, redirects EGF-Rs from lysosomes to the plasma membrane. Their ultrastructural analyses indicate that this is because endosome-to-lysosome trafficking of EGF-Rs is inhibited. Interestingly, cell proliferation is also inhibited under these circumstances. The balance between Rho-GG and Rho-F thus appears to control the fate of internalized EGF-R; the effect on cell proliferation might be an apoptotic/cytostatic response to a chronic trafficking defect.
Related articles in JCS:
- Farnesyltransferase inhibitors disrupt EGF receptor traffic through modulation of the RhoB GTPase
- Matthew Wherlock, Alexandra Gampel, Clare Futter, and Harry Mellor
JCS 2004 117: 3221-3231.
[Abstract]
[Full Text]
