Vangl2, the planner cell polarity protein, is complexed with postsynaptic density protein PSD‐95

Yoshioka, Toshinori; Hagiwara, Akari; Hida, Yamato; Ohtsuka, Toshihisa

doi:10.1016/j.febslet.2013.03.030

Cited by 26 publications

(29 citation statements)

References 32 publications

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“…As dendritic spines are the specific subcellular site of glutamatergic synapses in pyramidal neurons, these data are consistent with previous findings that Vangl2 localizes to the postsynaptic compartment of glutamatergic synapses, where it interacts with PSD95, transsynaptic adhesion molecules and the PCP pathway protein Prickle2 [14,15,16]. Our genetic data corroborate previous reports of similar phenotypes following shRNA-mediated knockdown of Vangl2 in cultured neurons [15,33] and have allowed us to compare and contrast neurodevelopmental phenotypes induced by two molecularly distinct (engineered null vs. spontaneous missense) alleles at this locus.…”

Section: Discussionsupporting

confidence: 92%

“…The four-pass transmembrane protein Van Gogh-like 2 (Vangl2) is a key player in the PCP pathway and interacts with several proteins that influence synapse formation, including other PCP proteins such as Dishevelled (Dvl) [12] and Dapper-antagonist of catenin-1 (Dact1) [13] as well as the postsynaptic protein PSD95 [14,15,16]. Vangl2 also participates in signaling upstream of small GTPases [17,18] regulating cytoskeletal dynamics crucial to dendrite and dendritic spine formation and plasticity [19,20,21,22].…”

Section: Introductionmentioning

confidence: 99%

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The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain

Okerlund

Stanley²,

Cheyette³

2016

Complex Psychiatry

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The transmembrane protein Vangl2, a key regulator of the Wnt/planar cell polarity (PCP) pathway, is involved in dendrite arbor elaboration, dendritic spine formation and glutamatergic synapse formation in mammalian central nervous system neurons. Cultured forebrain neurons from Vangl2 knockout mice have simpler dendrite arbors, fewer total spines, less mature spines and fewer glutamatergic synapse inputs on their dendrites than control neurons. Neurons from mice heterozygous for a semidominant Vangl2 mutation have similar but not identical phenotypes, and these phenotypes are also observed in Golgi-stained brain tissue from adult mutant mice. Given increasing evidence linking psychiatric pathophysiology to these subneuronal sites and structures, our findings underscore the relevance of core PCP proteins including Vangl2 to the underlying biology of major mental illnesses and their treatment.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain

Okerlund

Stanley²,

Cheyette³

2016

Complex Psychiatry

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“…Van Gogh and Fz affect neurite growth independently in Drosophila (54), and Van Gogh, Prickle, and Dishevelled mutant neurons in Caenorhabditis elegans display supernumerary neurites (62). An additional role of Vangl2 in synapse formation was recently demonstrated (63,64). These observations suggest that Vangl1,2 are likely to affect brain development by acting in different pathways, in addition to epithelial PCP.…”

Section: Discussionmentioning

confidence: 99%

Genetic evidence that Celsr3 and Celsr2 , together with Fzd3 , regulate forebrain wiring in a Vangl -independent manner

Huang

Feng

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Celsr3 and Fzd3, members of "core planar cell polarity" (PCP) genes, were shown previously to control forebrain axon guidance and wiring by acting in axons and/or guidepost cells. Here, we show that Celsr2 acts redundantly with Celsr3, and that their combined mutation mimics that of Fzd3. The phenotypes generated upon inactivation of Fzd3 in different forebrain compartments are similar to those in conditional Celsr2-3 mutants, indicating that Fzd3 and Celsr2-3 act in the same population of cells. Inactivation of Celsr2-3 or Fzd3 in thalamus does not affect forebrain wiring, and joint inactivation in cortex and thalamus adds little to cortical inactivation alone in terms of thalamocortical projections. On the other hand, joint inactivation perturbs strongly the formation of the barrel field, which is unaffected upon single cortical or thalamic inactivation, indicating a role for interactions between thalamic axons and cortical neurons in cortical arealization. Unexpectedly, forebrain wiring is normal in mice defective in Vangl1 and Vangl2, showing that, contrary to epithelial PCP, axon guidance can be Vangl independent in some contexts. Our results suggest that Celsr2-3 and Fzd3 regulate axonal navigation in the forebrain by using mechanisms different from classical epithelial PCP, and require interacting partners other than Vangl1-2 that remain to be identified.Cre | anterior commissure | internal capsule | cortical barrels

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“…Biochemical and molecular analyses revealed that Vangl2 binds directly to N-cadherin [198,199], the transmembrane protein that facilitates the initial critical adhesive event between presynaptic and postsynaptic elements, to mediate its endocytic removal from the membrane [199]. Vangl2 and Prickle2 also bind and promote postsynaptic clustering of PSD95, critical for maintenance of synaptic integrity [199,227,228]. Prickle1 was found to regulate synaptogenesis and synaptic vesicle trafficking through a direct interaction with synapsin1 (Syn1) [229]; the synapsin protein family have important roles in synapse formation and neurotransmitter release and have previously been implicated in the pathogenesis of psychiatric disorders [230,231,232,233,234,235,236].…”

Section: Synapse Formation and Functionmentioning

confidence: 99%

Neurodevelopmental Perspectives on Wnt Signaling in Psychiatry

Mulligan

Cheyette

2016

Complex Psychiatry

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Mounting evidence indicates that Wnt signaling is relevant to pathophysiology of diverse mental illnesses including schizophrenia, bipolar disorder, and autism spectrum disorder. In the 35 years since Wnt ligands were first described, animal studies have richly explored how downstream Wnt signaling pathways affect an array of neurodevelopmental processes and how their disruption can lead to both neurological and behavioral phenotypes. Recently, human induced pluripotent stem cell (hiPSC) models have begun to contribute to this literature while pushing it in increasingly translational directions. Simultaneously, large-scale human genomic studies are providing evidence that sequence variation in Wnt signal pathway genes contributes to pathogenesis in several psychiatric disorders. This article reviews neurodevelopmental and postneurodevelopmental functions of Wnt signaling, highlighting mechanisms, whereby its disruption might contribute to psychiatric illness, and then reviews the most reliable recent genetic evidence supporting that mutations in Wnt pathway genes contribute to psychiatric illness. We are proponents of the notion that studies in animal and hiPSC models informed by the human genetic data combined with the deep knowledge base and tool kits generated over the last several decades of basic neurodevelopmental research will yield near-term tangible advances in neuropsychiatry.

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Vangl2, the planner cell polarity protein, is complexed with postsynaptic density protein PSD‐95

Cited by 26 publications

References 32 publications

The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain

The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain

Genetic evidence that Celsr3 and Celsr2 , together with Fzd3 , regulate forebrain wiring in a Vangl -independent manner

Neurodevelopmental Perspectives on Wnt Signaling in Psychiatry

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