A role for noncanonical Wnt signaling in the maturation and morphogenesis of synapses

Actin polymerization by Formins such as Daam1leadstotheformation of Sumanirole Maleate linear as opposed to branched networks of F-Actin. Ultrastructural studies have shown that presynaptic boutons contain both linear and branched networks of F-Actin filaments. Linear Factin networks are thought to function in the translocation of SVs from the RP to the RRP situated close to the active zone, while branched F-actin networks have been implicated in bulk endocytosis of synaptic vesicle proteins after fusion. Given the exclusive localization of Piccolo at the active zone, and the predicted plus-endorientation of F-Actin filaments emanating from the active zone, the association of Daam1with Piccolo could facilitate the translocation of SVs via myosin motors toward their ultimate sites of docking and fusion. In addition to its direct role in Actin polymerization, Daam1 also independently activates RhoA GTPase activity. This suggests that a local pool of activated RhoA may result from Piccolo-Daam1 interactions. Activated RhoA interacts with effector proteins including protein kinases and actin-binding proteins, which directly and indirectly influence local assembly and disassembly of F-Actin. Interestingly, several studies have shown a role for noncanonical Wnt signaling in the maturation and morphogenesis of synapses, as well as in synaptic transmission, suggesting an important role for this system in sculpting synapses. Mechanistically, it Oxandrolone remains unclear what lies down stream of Wnt/Frizzled/Dishevelled, but Piccolo, through its interactions with Daam1,may impose a physiologically relevant spatial restriction on Daam1 dependent non-canonical Wnt signaling. Intriguingly, components of the Wnt/Frizzled/Dishevelled signaling complex are present both pre- and post synaptically at vertebrate synapses and Daam1 has been implicated in regulation of both axonal and dendritic growth as well as lateral asymmetry in the vertebrate brain. Localization of the Wnt signaling cascade via Piccolo anchoring of Daam1 may, therefore, be important for coordinating pre and post-synaptic Wnt signals. In addition to Daam1, Piccolo has other binding partners that are involved in Actin assembly.

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