Kinesin<i>Kif3b</i>mutation reduces<scp>NMDAR</scp>subunit<scp>NR</scp>2A trafficking and causes schizophrenia‐like phenotypes in mice

Al-Sabban, A.H.; Morikawa, Momo; Tanaka, Yosuke; Takei, Yosuke; Hirokawa, Nobutaka

doi:10.15252/embj.2018101090

Cited by 49 publications

(43 citation statements)

References 77 publications

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“…KIF3B protein is involved in the transport of NR2A vesicles to N-methyl-d-aspartate receptors (NMDAR), which is crucial for neuronal plasticity and synapse formation. KIF3B plays an important role in the electrophysiological response of NMDAR and hence synaptic plasticity, which is one of the pathogenetic concepts of schizophrenia [72]. Although the presented studies concern the animal model, they are of great importance in patients with schizophrenia who were identified with KIF3B mutations.…”

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confidence: 99%

Oxidative-Antioxidant Imbalance and Impaired Glucose Metabolism in Schizophrenia

et al. 2020

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Schizophrenia is a neurodevelopmental disorder featuring chronic, complex neuropsychiatric features. The etiology and pathogenesis of schizophrenia are not fully understood. Oxidative-antioxidant imbalance is a potential determinant of schizophrenia. Oxidative, nitrosative, or sulfuric damage to enzymes of glycolysis and tricarboxylic acid cycle, as well as calcium transport and ATP biosynthesis might cause impaired bioenergetics function in the brain. This could explain the initial symptoms, such as the first psychotic episode and mild cognitive impairment. Another concept of the etiopathogenesis of schizophrenia is associated with impaired glucose metabolism and insulin resistance with the activation of the mTOR mitochondrial pathway, which may contribute to impaired neuronal development. Consequently, cognitive processes requiring ATP are compromised and dysfunctions in synaptic transmission lead to neuronal death, preceding changes in key brain areas. This review summarizes the role and mutual interactions of oxidative damage and impaired glucose metabolism as key factors affecting metabolic complications in schizophrenia. These observations may be a premise for novel potential therapeutic targets that will delay not only the onset of first symptoms but also the progression of schizophrenia and its complications.

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confidence: 99%

Oxidative-Antioxidant Imbalance and Impaired Glucose Metabolism in Schizophrenia

et al. 2020

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“…Recent work has shown that KIF3B may be involved in the trafficking of the NMDAR subunit, NR2A (Alsabban et al, 2020). In this work, KIF3B knockdown showed a contrasting phenotype, namely a reduction in spine density, stubby spines, and PSD-95 expression.…”

Section: Discussionmentioning

confidence: 70%

Molecular Motor KIF3B Acts as a Key Regulator of Dendritic Architecture in Cortical Neurons

Joseph

Grinman

Swarnkar

et al. 2020

Front. Cell. Neurosci.

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Neurons require a well-coordinated intercellular transport system to maintain their normal cellular function and morphology. The kinesin family of proteins (KIFs) fills this role by regulating the transport of a diverse array of cargos in post-mitotic cells. On the other hand, in mitotic cells, KIFs facilitate the fidelity of the cellular division machinery. Though certain mitotic KIFs function in post-mitotic neurons, little is known about them. We studied the role of a mitotic KIF (KIF3B) in neuronal architecture. We find that the RNAi mediated knockdown of KIF3B in primary cortical neurons resulted in an increase in spine density; the number of thin and mushroom spines; and dendritic branching. Consistent with the change in spine density, we observed a specific increase in the distribution of the excitatory post-synaptic protein, PSD-95 in KIF3B knockdown neurons. Interestingly, overexpression of KIF3B produced a reduction in spine density, in particular mushroom spines, and a decrease in dendritic branching. These studies suggest that KIF3B is a key determinant of cortical neuron morphology and that it functions as an inhibitory constraint on structural plasticity, further illuminating the significance of mitotic KIFs in post-mitotic neurons.

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“…Interestingly, dissociated hippocampal cultures from KIF3B +/- mice showed a pronounced axonal phenotype. The growth cones of KIF3B +/- neurons were significantly enlarged [ 47 ]. The number of filopodia on the growth cone was decreased in KIF3B +/- neurons [ 47 ].…”

Section: Structural Plasticitymentioning

confidence: 99%

“…The growth cones of KIF3B +/- neurons were significantly enlarged [ 47 ]. The number of filopodia on the growth cone was decreased in KIF3B +/- neurons [ 47 ]. The immature arrest of the growth cone may be the cause of the miniature neurites observed with KIF3B knockout.…”

Section: Structural Plasticitymentioning

confidence: 99%

“…These organelles were transported predominately in an anterograde fashion via fast axonal transport [ 44 , 65 ]. Recent work has shown that KIF3B also traffics NR2A to the synapse [ 47 ]. Experiments such as proteomic analyses of kinesin complexes have yet to be done to identify the cargos of KIF3B, 11, and other mitotic kinesins to elucidate their role in cargo transport.…”

Section: Transportmentioning

confidence: 99%

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Double Duty: Mitotic Kinesins and Their Post-Mitotic Functions in Neurons

Joseph

Swarnkar

Puthanveettil

2021

Cells

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Neurons, regarded as post-mitotic cells, are characterized by their extensive dendritic and axonal arborization. This unique architecture imposes challenges to how to supply materials required at distal neuronal components. Kinesins are molecular motor proteins that mediate the active delivery of cellular materials along the microtubule cytoskeleton for facilitating the local biochemical and structural changes at the synapse. Recent studies have made intriguing observations that some kinesins that function during neuronal mitosis also have a critical role in post-mitotic neurons. However, we know very little about the function and regulation of such kinesins. Here, we summarize the known cellular and biochemical functions of mitotic kinesins in post-mitotic neurons.

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KinesinKif3bmutation reducesNMDARsubunitNR2A trafficking and causes schizophrenia‐like phenotypes in mice

Cited by 49 publications

References 77 publications

Oxidative-Antioxidant Imbalance and Impaired Glucose Metabolism in Schizophrenia

Oxidative-Antioxidant Imbalance and Impaired Glucose Metabolism in Schizophrenia

Molecular Motor KIF3B Acts as a Key Regulator of Dendritic Architecture in Cortical Neurons

Double Duty: Mitotic Kinesins and Their Post-Mitotic Functions in Neurons

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