The Rho family GTPases control diverse cellular processes through a large group of effector mlecules, which elicit specific physiological responses. On p. 567, Kozo Kaibuchi's group identify a novel member of the IQGAP family of Rho family effectors, IQGAP3. They demonstrate that it interacts with and functions as an effector for the activated Rho GTPases Rac1 and Cdc42. Furthermore, they show that it directly associates with actin filaments in vivo through its N-terminal calponin homology domain (CHD). IQGAP3 is highly expressed in the brain and localises to the distal tips of axons in hippocampal neurons. Using an siRNA approach the authors demonstrate that IQGAP3, unlike IQGAP1, is necessary for neurite outgrowth in PC12 cells in response to nerve growth factor (NGF) and show that this functional difference between IQGAP1 and IQGAP3 resides within the C-teminal region. Furthermore, they establish that IQGAP3 is vital for Rac1/Cdc42-directed hippocampal axon outgrowth. This study reveals that IQGAPs regulate neuronal cell morphology via their ability to organise the cytoskeleton and stabilise activated Rac1 and Cdc42 and identifies a specific role for IQGAP3 in axonal elongation.
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