8.03.2006

Let's inhibit Cdc42

Secramine inhibits Cdc42-dependent functions in cells and Cdc42 activation in vitro.
HE Pelish, JR Peterson, SB Salvarezza, E Rodriguez-Boulan, JL Chen, M Stamnes, E Macia, Y Feng, MD Shair, and T Kirchhausen
Nat Chem Biol, Jan 2006; 2(1): 39-46

Cdc42 is a small GTPase associated with multiple cellular functions. It is "active" when is bound to GTP and membranes, and "inactive" when bound to GDP. This and other small GTPases are further regulated by RhoGDI, which regulates Cdc42 binding to membranes.

The paper I picked describes a small molecule - Secramine - that interferes with Cdc42-related activities, therefore it can be used as an inhibitor of Cdc42. The authors found that secramine does not interfere with the loading of GTP into Cdc42. Instead, secramine seems to interfere with membrane-dependent activation of Cdc42, probably by stabilizing the interaction between Cdc42 and RhoGDI. Further work is probably on the way to characterize the mechanism of action of secramine, but in the mean time the authors showed that secramine inhibited transport of NCAM from the golgi to the plasma membrane and golgi reorientation in migrating cells. These two cellular processes are known to be dependent on Cdc42. Secramine can be a very powerfull tool to use as a reversible inhibitor of Cdc42.

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