Motility to Synapse Format

ipropriate neurons is essential for the development of functional neural networks. In the mammalian CNS, formation of glutama-tergic synaptic inputs is characterized by an early phase of slow addition followed by a burst of synaptogenesis, ending in maturation and pruning of contacts (Goda and Davis, 2003; Waites et al., 2005). Coinciding with this rapid phase of synapse addition is the presence of thin, elongated filopodia-like protru-sions on dendrites. In vitro and in vivo studies have demon-strated that these dendritic filopodia are highly dynamic struc-tures, capable of exploring their local cellular environment and possibly initiating contact with appropriate presynaptic partners (Dailey and Smith, 1996; Fiala et al., 1998; Lendvai et al., 2000; kinase-dependent manner to phosphorylate guanine exchange factors (GEFs) such as Tiam1, kalirin-7, and intersectin, that cat-alyze the Rho family GTPases Rac1 and Cdc42 into the active state (Irie and Yamaguchi, 2002; Penzes et al., 2003; Tolias et al., 2007). EphB2 also phosphorylates the transmembrane heparan sulfate proteoglycan syndecan-2 (Ethell et al., 2001). Each of these signaling pathways activates molecules that lead to reorganization of the actin cytoskeleton and spine morpho-genesis. For example, phosphorylation of kalirin-7 and activation of Rac1 cause phosphorylation of p21-activated kinase (PAK), while syndecan-2 appears to work coordinately with intersec-tion/Cdc42 to activate N-WASP and the Arp2/3 complex (IrieEphB Receptors Couple D