Synaptojanin 2, a novel Rac1 effector that regulates clathrin-mediated endocytosis

The small GTPase Rac has been implicated in a wide range of cellular proces ses, including the organization of the actin cytoskeleton, transcriptional control and endocytic vesicle trafficking [1-3], The signaling components t hat mediate these functions downstream of Rac largely remain to be identifi ed. In this study, we have identified synaptojanin 2, a polyphosphoinositid e phosphatase as a novel Rac1 effector. Synaptojanin 2 directly and specifi cally interacts with Rad in a GTP-dependent manner. Expression of constitut ively active Rac1 caused the translocation of synaptojanin 2 from the cytop lasm to the plasma membrane. Both activated Rad and a membrane-targeted ver sion of synaptojanin 2 inhibited endocytosis of the epidermal growth factor (EGF) and transferrin receptors, a process that is known to be dependent o n polyphosphoinositide lipids. Endocytosis of growth factor receptors is th ought to play an important role in the regulation of cell proliferation. Th us, these results suggest that synaptojanin 2 may mediate the inhibitory ef fect of Rac1 on endocytosis and could contribute to Rac1-mediated control o f cell growth.