Long-term changes in synaptic strength, such as those which occur during long-term depression (LTD) and long-term potentiation (LTP) are thought to underlie learning and memory. A key event in both LTP and LTD is the change in the number of AMPA-type glutamate receptors (AMPARs) expressed at the postsynaptic membrane, which is accomplished through activity-dependent regulation of receptor exocytosis and endocytosis. The Activity-regulated cytoskeleton-associated protein, Arc, promotes endocytosis of AMPA type glutamate receptors and regulates cytoskeletal assembly in neuronal dendrites. Both of these functions may be mediated by its reported interaction with dynamin 2 (Dyn2) (Chowdhury et al., 2006, Neuron 52, 445-459), a large GTPase that participates in receptor-mediated endocytosis, actin polymerization, and microtubule stabilization. Here we present evidence that Arc accelerates the polymerization of Dyn2 and stabilizes Dyn2 polymers against GTP-dependent disassembly. As a result of this stabilization, Arc prolongs assembly-dependent GTP hydrolysis catalysed by Dyn2. Arc also prolongs the high GTPase activity state of Dyn3, an isoform of dynamin implicated in dendrite remodeling and in stabilization of clathrin-coated pits near the postsynaptic density, but not that of Dyn1, a neuron-specific isoform involved in synaptic vesicle recycling. We further show in this study that Arc has a tendency to form large soluble aggregates, which may function as a scaffold for dynamin assembly and self-activation.This work was supported by National Institutes of Health grant GM076665 (DMJ)