| 1 | J. Neurosci. 2014 Oct 34: 13725-36 |
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| PMID | 25297099 |
| Title | The schizophrenia susceptibility gene dysbindin regulates dendritic spine dynamics. |
| Abstract | Dysbindin is a schizophrenia susceptibility gene required for the development of dendritic spines. The expression of dysbindin proteins is decreased in the brains of schizophrenia patients, and neurons in mice carrying a deletion in the dysbindin gene have fewer dendritic spines. Hence, dysbindin might contribute to the spine pathology of schizophrenia, which manifests as a decrease in the number of dendritic spines. The development of dendritic spines is a dynamic process involving formation, retraction, and transformation of dendritic protrusions. It has yet to be determined whether dysbindin regulates the dynamics of dendritic protrusions. Here we address this question using time-lapse imaging in hippocampal neurons. Our results show that dysbindin is required to stabilize dendritic protrusions. In dysbindin-null neurons, dendritic protrusions are hyperactive in formation, retraction, and conversion between different types of protrusions. We further show that CaMKII? is required for the stabilization of mushroom/thin spines, and that the hyperactivity of dendritic protrusions in dysbindin-null neurons is attributed in part to decreased CaMKII? activity resulting from increased inhibition of CaMKII? by ABI1. These findings elucidate the function of dysbindin in the dynamic morphogenesis of dendritic protrusions, and reveal the essential roles of dysbindin and CaMKII? in the stabilization of dendritic protrusions during neuronal development. |
| SCZ Keywords | schizophrenia |
| 2 | Neuroreport 2016 Feb 27: 145-50 |
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| PMID | 26691754 |
| Title | Decreased expression of cortactin in the schizophrenia brain. |
| Abstract | schizophrenia is a severe psychiatric disorder that is characterized by a wide array of symptoms and a complex neuropathology. A well-characterized neurobiological feature of schizophrenia is abnormal synaptic plasticity, although the mechanisms underlying this are not fully understood. Numerous studies have demonstrated a link between proper functioning of the cytoskeleton and synaptic plasticity. The actin-related protein-2/3 (Arp2/3) complex is responsible for the nucleation of new actin filaments and elongation of existing actin filaments and is thus crucial to cytoskeletal dynamics, especially actin polymerization and organization. To determine whether the Arp2/3 complex is abnormally expressed in schizophrenia, we measured the protein expression of Arp2 and Arp3, as well as Arp2/3 complex binding partners and associated proteins including cortactin, neuronal-Wiskott-Aldrich syndrome protein (WASP), WASP-family verprolin homologous protein 1 (WAVE1), and Abelson interactor 1 (ABI1) in the superior temporal gyrus of paired schizophrenia and comparison participants. No changes were found in Arp2, Arp3, neuronal-WASP, WAVE1, or ABI1. However, all three isoforms of cortactin were decreased in schizophrenia. Specifically, the 62 kDa isoform was decreased by 43%; the 71 kDa isoform was decreased by 32%; and the 58 kDa isoform was decreased by 35%. Cortactin regulates branching of filamentous actin through its binding and activation of the Arp2/3 complex, and it is thus critical to the formation of stable actin networks. These findings contribute to a growing body of evidence implicating altered cytoskeletal dynamics in schizophrenia. |
| SCZ Keywords | schizophrenia |