2017
DOI: 10.1016/j.neuron.2016.12.006
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TAOK2 Kinase Mediates PSD95 Stability and Dendritic Spine Maturation through Septin7 Phosphorylation

Abstract: SUMMARY Abnormalities in dendritic spines are manifestations of several neurodevelopmental and psychiatric diseases. TAOK2 is one of the genes in the 16p11.2 locus, copy number variations of which are associated with autism and schizophrenia. Here, we show that the kinase activity of the serine/threonine kinase encoded by TAOK2 is required for spine maturation. TAOK2 depletion results in unstable dendritic protrusions, mislocalized shaft-synapses, and loss of compartmentalization of NMDA receptor-mediated calc… Show more

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Cited by 119 publications
(138 citation statements)
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“…Using PREM, we also detected septin7 at the spine base, consistent with previously reported light microscopy data (Tada et al, 2007;Xie et al, 2007). Interestingly, perturbations of septin functions result in somewhat similar dendritic phenotypes (Tada et al, 2007;Xie et al, 2007;Yadav et al, 2017), suggesting that ␤III spectrin and septins may also cooperate for shaping the spine neck.…”
Section: Discussionsupporting
confidence: 89%
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“…Using PREM, we also detected septin7 at the spine base, consistent with previously reported light microscopy data (Tada et al, 2007;Xie et al, 2007). Interestingly, perturbations of septin functions result in somewhat similar dendritic phenotypes (Tada et al, 2007;Xie et al, 2007;Yadav et al, 2017), suggesting that ␤III spectrin and septins may also cooperate for shaping the spine neck.…”
Section: Discussionsupporting
confidence: 89%
“…Periodicity of ␤III spectrin was noted only in occasional small regions of dendrites (Zhong et al, 2014). Although with some imagination one can suppose a ϳ200 nm periodicity of ␤III spectrin immunogold distribution in the dendritic spine in Figure 4D, we so far were unable to reliably detect actin or ␤IV spectrin periodicity in neurons by immunogold PREM (Jones et al, 2014), possibly because of high complexity of PREM images compared with computationally simplified subdiffraction images.…”
Section: Discussionmentioning
confidence: 86%
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“…Aberrations in dendritic spines were detected in various neurodegenerative and psychiatric diseases manifesting perturbations in cognition and information processing (Yadav et al ., 2017). PSD95 is a scaffolding protein involved in the assembly and function of the postsynaptic density complex as well as required for spine stability.…”
Section: Resultsmentioning
confidence: 99%
“…45 Our findings suggest that LAT, like CD247 and ZAP70, [41][42][43][44] plays a role in neurogenesis and that perturbation of this pathway may lead to neurodevelopmental phenotypes. They also provide an interesting example of the non-random organization of the genome 61 as gene dosage modification of (at least) one and five of the 9 and 28 genes mapping within the 220 kb BP2-BP3 and 600 kb BP4-BP5 intervals can influence the PTEN-antagonized (phosphatase and tensin homolog) PI3K/AKT and Ras/MAPK pathways: LAT, TAOK2, that encodes a PTEN-binding MAP kinase kinase kinase essential for dendrite morphogenesis, 62,63 MVP, the product of which interacts with PTEN and regulates its intracellular localization, 59,64,65 MAPK3, KCTD13, 37 and CDIPT (MIM: 605893) encoding an enzyme of the phosphatidylinositol synthesis pathway. Consistent with this view, the genes differentially expressed in cell lines of 16p11.2 600 kb BP4-BP5 carriers were enriched not only in pathways relevant to neurodevelopmental defects and ciliopathy but also in genes involved in phosphoinositide signaling.…”
Section: Discussionmentioning
confidence: 99%