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The Journal of Neuroscience, November 16, 2005, 25(46):10627-10636; doi:10.1523/JNEUROSCI.1947-05.2005
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Cellular/Molecular
Rac1 Induces the Clustering of AMPA Receptors during Spinogenesis
Katie M. Wiens, Hang Lin, andDezhi Liao Department of Neuroscience, The University of Minnesota, Minneapolis, Minnesota 55455
Glutamatergic synapses switch from nonspiny synapses to become dendritic spines during early neuronal development. Here, we report that the lack of sufficient Rac1, a small RhoGTPase, contributes to the absence of spinogenesis in immature neurons. The overexpression of green fluorescence protein-tagged wild-type Rac1 initiated the formation of dendritic spines in cultured dissociated hippocampal neurons younger than 11 d in vitro, indicating that Rac1 is likely one of the missing pieces responsible for the lack of spines in immature neurons. The overexpression of wild-type Rac1 also induced the clustering of AMPA receptors (AMPARs) and increased the amplitude of miniature EPSCs (mEPSCs). The expression of constitutively active Rac1 induced the formation of unusually large synapses with large amounts of AMPAR clusters. Also, our live imaging experiments revealed that the contact of an axon induced the clustering of Rac1, and subsequent morphological changes led to spinogenesis. Additionally, the overexpression of wild-type Rac1 and constitutively active Rac1 increased the size of preexisting spines and the amplitude of mEPSCs in mature neurons (>21 d in vitro) within 24 h after transfection. Together, these results indicate that activation of Rac1 enhances excitatory synaptic transmission by recruiting AMPARs to synapses during spinogenesis, thus providing a mechanistic link between presynaptic and postsynaptic developmental changes. Furthermore, we show that Rac1 has two distinct roles at different stages of neuronal development. The activation of Rac1 initiates spinogenesis at an early stage and regulates the function and morphology of preexisting spines at a later stage.
Key words: synaptogenesis; Rac1; glutamate receptor; dendritic spine; AMPA receptor; synaptic plasticity; Rho GTPase
Received May 16, 2005; revised October 5, 2005; accepted October 5, 2005.
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