156. Reduced Dysbindin Protein and Behavioral Abnormalities in Mice with a Single Point Mutation on the Schizophrenia Risk Gene DTNBP1

Chang, Eric H.; Yeung, Lok Wan; Chandon, T.‐S. S.; Barbari, Kristina; Fernando, Kayla; Malhotra, Anil K.

doi:10.1016/j.biopsych.2017.02.169

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“…; Chang et al . ). Also, dysbindin is involved in neurite outgrowth in differentiated neuroblastoma cells and primary neurons (Kubota et al .…”

Section: Discussionmentioning

confidence: 97%

“…Decreased dysbindin stability has been reported to have correlation with schizophrenia (Weickert et al 2008;Chang et al 2017). Also, dysbindin is involved in neurite outgrowth in differentiated neuroblastoma cells and primary neurons (Kubota et al 2009;Ghiani et al 2010;Ito et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Dysbindin has been suggested as a positional risk gene of schizophrenia (Millar et al 2000;Van Den Bogaert et al 2003). In the brains of schizophrenic patients, the protein and messenger RNA (mRNA) expression levels of dysbindin were lowered (Weickert et al 2008;Chang et al 2017). Genetic studies also have associated dysbindin with schizophrenia (Tang et al 2003;Owen et al 2004).…”

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confidence: 99%

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Vaccinia‐related kinase 2 modulates role of dysbindin by regulating protein stability

Jeong

Choi

Lee

et al. 2018

Journal of Neurochemistry

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Vaccinia-related kinase 2 (VRK2) is a serine/threonine kinase that belongs to the casein kinase 1 family. VRK2 has long been known for its relationship with neurodegenerative disorders such as schizophrenia. However, the role of VRK2 and the substrates associated with it are unknown. Dysbindin is known as one of the strong risk factors for schizophrenia. The expression of dysbindin is indeed significantly reduced in schizophrenia patients. Moreover, dysbindin is involved in neurite outgrowth and regulation of NMDA receptor signaling. Here, we first identified dysbindin as a novel interacting protein of VRK2 through immunoprecipitation. We hypothesized that dysbindin is phosphorylated by VRK2 and further that this phosphorylation plays an important role in the function of dysbindin. We show that VRK2 phosphorylates Ser 297 and Ser 299 of dysbindin using in vitro kinase assay. In addition, we found that VRK2-mediated phosphorylation of dysbindin enhanced ubiquitination of dysbindin and consequently resulted in the decrease in its protein stability through western blotting. Over-expression of VRK2 in human neuroblastoma (SH-SY5Y) cells reduced neurite outgrowth induced by retinoic acid. Furthermore, a phosphomimetic mutant of dysbindin alleviated neurite outgrowth and affected surface expression of N-methyl-d-aspartate 2A, a subunit of NMDA receptor in mouse hippocampal neurons. Together, our work reveals the regulation of dysbindin by VRK2, providing the association of these two proteins, which are commonly implicated in schizophrenia. Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/.

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“…; Chang et al . ). Also, dysbindin is involved in neurite outgrowth in differentiated neuroblastoma cells and primary neurons (Kubota et al .…”

Section: Discussionmentioning

confidence: 97%