“It is well established that the developing nervous system


“It is well established that the developing nervous system requires the combined activities of synapse S3I-201 ic50 formation and elimination (Goda and Davis, 2003 and Luo and O’Leary, 2005), and there is increasing evidence that this is also true for the maintenance of mature neural circuitry (Holtmaat and Svoboda, 2009 and Xu et al., 2009). The molecular mechanisms that control synapse formation have been studied extensively and include modulation of the neuronal cytoskeleton, target recognition, synapse assembly, and stabilization (Luo, 2002, Goda and Davis, 2003 and Datwani et al., 2009). The opposing mechanisms that disassemble synaptic connections are beginning to emerge and include modulation

of growth factor signaling, the submembranous spectrin/ankyrin skeleton, cell adhesion and cellular mechanisms that dismantle the neuronal membrane (Luo and O’Leary, 2005, Nikolaev et al., 2009, Koch et al., 2008, Pielage et al., 2005, Pielage et al., 2008, Watts et al., 2003 and Massaro et al., 2009). In general these different molecular mechanisms are studied in isolation. Yet it is also clear that the phenomena

of synapse formation and retraction can coexist within the terminals of single neurons (Walsh and Lichtman, 2003). The mechanisms that serve to balance synapse stabilization and elimination within a neuron to achieve and maintain precise patterns of neural connectivity remain unknown. To date, relatively few molecular mechanisms have MDV3100 been uncovered that participate in both synapse formation and elimination. Any such signaling system might reasonably be a point of control to balance synapse growth and elimination. Growth factor signaling is a type of global regulation that coordinates synapse formation and elimination with neuronal size (Huang and Reichardt, 2001). However, much less is known about how a balance between synapse stability and growth might be organized and executed locally within a nerve terminal. Potential candidates include adaptive immune signaling

(Datwani et al., 2009) and control of cell adhesion. Remarkably, local regulators of the actin and microtubule cytoskeletons over capable of balancing growth and elimination have yet to be clearly defined. Here, we provide evidence that the actin-capping, spectrin-binding protein Adducin participates in both actin dependent synaptic growth and synapse stabilization. As such, Adducin may serve to coordinate these opposing activities that normally specify the shape, extent, and stability of the presynaptic terminal. The vertebrate genome encodes the three closely related adducin genes α-adducin, β-adducin, and γ-adducin that form tetramers composed of either α/β- or α/γ-heterodimers ( Matsuoka et al., 2000). Adducin is a key protein involved in the assembly of the sub-membranous Spectrin-actin network ( Bennett and Baines, 2001).

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