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Review
. 2011 Feb;21(1):151-9.
doi: 10.1016/j.conb.2010.12.002. Epub 2011 Jan 14.

Wnt signaling during synaptic development and plasticity

Vivian Budnik  1 , Patricia C Salinas
Affiliations
Review

Wnt signaling during synaptic development and plasticity

Vivian Budnik et al. Curr Opin Neurobiol. 2011 Feb.

Abstract

The formation of synaptic connections requires a dialogue between pre and postsynaptic cells to coordinate the assembly of the presynaptic release machinery and the postsynaptic receptive complexes. Signaling molecules of the Wnt family of proteins are central to this trans-synaptic dialogue. At the neuromuscular junction and central synapses, Wnts promote synaptic assembly by signaling to the developing pre and postsynaptic compartments. In addition, new studies reveal that expression of Wnt proteins and localization of their Fz receptors are regulated by neuronal activity. Importantly, Wnts mediates the synaptic changes induced by patterned neuronal activity or sensory experience in mature neurons. Here we review recent findings into the function of Wnt signaling at the synapse and its link to activity-dependent synaptic growth and function.

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Figures

Figure 1
Figure 1
Illustration of the role of Wnts in the assembly of synapses. Wnt7a through Fz5 and Dvl1 inhibits GSK-3β to promote the assembly of the presynaptic terminal. Inhibition of GSK-3β stimulates the recruitment of synaptic vesicles and active zone proteins such as Bassoon. Wnt5a, in contrast, acts on the postsynaptic side to increase clustering of PSD95. Wnt5a also increases the expression and clustering of GABAaR receptor on the dendritic shaft. The receptors for Wnt5a remain to be identified.
Figure 2
Figure 2
Neuronal activity regulates synaptic localization of surface Fz5. Under control condition, a fraction of surface Fz5 is present at synaptic sites labelled with vGlut1 and NR1. High frequency stimulation (HFS) promotes the trafficking of Fz5 to the cell surface and also its localization to synapses (arrows). Blockade of endogenous Wnts with the CRD domain of Fz5 suppresses the mobilization of Fz5 to the cell surface and to synapse. Remarkable, blockade of endogenous Wnts also suppresses activity-mediated synaptogenesis.
Figure 3
Figure 3
Wg secreted from presynaptic motor neuron endings, binds to Fz-2 and co-receptor Arrow, which are localized presynaptically and postsynaptically. In the presynaptic cell, Wg activates a Divergent Canonical Wnt Pathway, involving Dvl activation, inhibition of GSK-3β activity and the regulation of the microtubule cytoskeleton through Futsch. In the postsynaptic cell, Wg activates the Frizzled Nuclear Import Pathway, which involves the cleavage and nuclear import of Fz-2. GRIP is required for the trafficking of receptors from the postsynaptic membrane towards the nucleus. WNT5 is also released from the presynaptic boutons and binds to its receptor Derailed (DRL) on the postsynaptic membrane to regulate synaptic bouton growth.
Figure 4
Figure 4
(a) Wnt11r induces AChR preclustering before innervation through interactions with MuSK and LRP4. In mice, Wnt3 might also regulate this process. (b) Wnt3 collaborates with Agrin in the formation of AChR clusters after muscle innervation.
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References

    1. van Amerongen R, Nusse R. Towards an integrated view of Wnt signaling in development. Development. 2009;136:3205–3214. This is a comprehensive review on Wnt signaling that considers the integration of different cascades rather than the old view of distinct linear pathways. - PubMed
    1. Salinas PC. Retrograde signalling at the synapse: a role for Wnt proteins. Biochem Soc Trans. 2005;33:1295–1298. - PubMed
    1. Speese SD, Budnik V. Wnts: up-and-coming at the synapse. Trends Neurosci. 2007;30:268–275. - PMC - PubMed
    1. De Ferrari GV, Papassotiropoulos A, Biechele T, Wavrant De-Vrieze F, Avila ME, Major MB, Myers A, Saez K, Henriquez JP, Zhao A, et al. Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer’s disease. Proc Natl Acad Sci U S A. 2007;104:9434–9439. - PMC - PubMed
    1. Zhao C, Aviles C, Abel RA, Almli CR, McQuillen P, Pleasure SJ. Hippocampal and visuospatial learning defects in mice with a deletion of frizzled 9, a gene in the Williams syndrome deletion interval. Development. 2005;132:2917–2927. - PubMed

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