Localization of nectin-2δ at perivascular astrocytic endfoot processes and degeneration of astrocytes and neurons in nectin-2 knockout mouse brain

Miyata, Muneaki; Mandai, Kenji; Maruo, Tomohiko; Sato, Junya; Shiotani, Hajime; Kaito, Aika; Yu, I.; Wang, Shujie; Fujiwara, Takeshi; Mizoguchi, Akira; Takai, Yoshimi; Rikitake, Yoshiyuki

doi:10.1016/j.brainres.2016.08.023

Cited by 24 publications

(43 citation statements)

References 51 publications

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“…The nectin‐2 gene was originally cloned as a murine homolog of the poliovirus receptor gene (Morrison & Racaniello, ), but its gene product was later shown to serve as an entry receptor for herpes simplex virus (Warner et al, ). In the preceding study, we showed that nectin‐2α is expressed in both cultured mouse neurons and astrocytes whereas nectin‐2δ is selectively expressed in cultured astrocytes (Miyata et al, ). In immunofluorescence microscopy on the mouse brain, nectin‐2α and/or nectin‐2δ (nectin‐2α/δ) is observed intensively in the pia mater, walls of the lateral ventricles, the choroid plexus, and the habenula in the forebrain.…”

Section: Introductionmentioning

confidence: 95%

Localization of nectin‐2α at the boundary between the adjacent somata of the clustered cholinergic neurons and its regulatory role in the subcellular localization of the voltage‐gated A‐type K⁺ channel Kv4.2 in the medial habenula

Shiotani

Miyata

et al. 2018

J of Comparative Neurology

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The medial habenula (MHb), implicated in stress, depression, memory, and nicotine withdrawal syndromes, receives septal inputs and sends efferents to the interpeduncular nucleus. We previously showed that the immunoglobulin-like cell adhesion molecules (CAMs) nectin-2α and nectin-2δ are expressed in astrocytes in the brain, but their expression in neurons remains unknown. We showed here by immunofluorescence microscopy that nectin-2α, but not nectin-2δ, was prominently expressed in the cholinergic neurons in the developing and adult MHbs and localized at the boundary between the adjacent somata of the clustered cholinergic neurons where the voltage-gated A-type K channel Kv4.2 was localized. Analysis by immunoelectron microscopy on this boundary revealed that Kv4.2 was localized at the membrane specializations (MSs) with plasma membrane darkening in an asymmetrical manner, whereas nectin-2α was localized on the apposed plasma membranes mostly at the outside of these MSs, but occasionally localized at their edges and insides. Nectin-2α at this boundary was not colocalized with the nectin-2α-binding protein afadin, other CAMs, or their interacting peripheral membrane proteins, suggesting that nectin-2α forms a cell adhesion apparatus different from the Kv4.2-associated MSs. Genetic ablation of nectin-2 delayed the localization of Kv4.2 at the boundary between the adjacent somata of the clustered cholinergic neurons in the developing MHb. These results revealed the unique localization of nectin-2α and its regulatory role in the localization of Kv4.2 at the MSs in the MHb.

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Section: Introductionmentioning

confidence: 95%

Localization of nectin‐2α at the boundary between the adjacent somata of the clustered cholinergic neurons and its regulatory role in the subcellular localization of the voltage‐gated A‐type K⁺ channel Kv4.2 in the medial habenula

Shiotani

Miyata

et al. 2018

J of Comparative Neurology

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“…In contrast to them, the Group 4, 6 and 7 proteins, of which expression levels were not markedly changed from P14, showed subtle difference in the regional expression levels. Furthermore, nectin-1, nectin-2, nectin-3 and afadin play crucial roles in development of the cerebral cortex and hippocampus (Gil-Sanz et al 2013Yamamoto et al 2015;Miyata et al 2016Miyata et al , 2017. For example, nectin-1, nectin-3 and afadin play important roles in the formation of the hippocampal mossy fiber synapse (Honda et al 2006;Toyoshima et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, nectin-1 regulates the branching of the olfactory mitral dendrites (Fujiwara et al 2015). Furthermore, nectin-1, nectin-2, nectin-3 and afadin play crucial roles in development of the cerebral cortex and hippocampus (Gil-Sanz et al 2013Yamamoto et al 2015;Miyata et al 2016Miyata et al , 2017.…”

Section: Discussionmentioning

confidence: 99%

Aging‐dependent expression of synapse‐related proteins in the mouse brain

et al. 2017

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A synapse is a cell adhesion structure that permits a neuron to pass a chemical or electrical signal to another neuron. They connect neurons and form neural networks that are essential for brain functions, such as learning and memory. At a chemical synapse, the presynapse and the postsynapse are connected by cell adhesion molecules. The presynapse contains synaptic vesicles and their release machinery, whereas the postsynapse contains postsynaptic densities and receptors for the neurotransmitters. Many proteins constituting a synapse have been identified, but their life-span expression profiles remain elusive. Here, we investigated the expression levels of representative synapse-related proteins by Western blot using the extranuclear supernatant fraction of the brains of mice at various ages. These proteins were classified into seven groups depending on their expression profiles during the embryonic stage, those from postnatal day 6 (P6) to P30, and those after P90. The expression levels of the majority of the proteins were gradually increased from the embryonic stage and then decreased at P14 or P30. After P90, the expression levels were not markedly changed or, in some proteins, increased. These results indicate that the expression levels of the synapse-related proteins are regulated orderly in an aging-dependent manner.

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“…In addition to its role in viral entry, GAS6 promotes oligodendrogenesis and myelination in the adult nervous system (52) and acts as a neurotrophic factor during hippocampal development (53). NECTIN2 is necessary for neuronal and glial survival (54). Cell-type enrichment analyses using human single-nucleus RNA-13 14 seq data from PsychEncode (45) was performed using EWCE (44).…”

Section: Maternal Immune Activation Induces Brain Transcriptomic Chanmentioning

confidence: 99%

Alterations in retrotransposition, synaptic connectivity, and myelination implicated by transcriptomic changes following maternal immune activation in non-human primates

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Gandal

Estes

et al. 2020

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Alterations in retrotransposition, synaptic connectivity, and myelination implicated by transcriptomic changes following maternal immune activation in non-human primates Nicholas F. AbstractBackground: Maternal immune activation (MIA) is a proposed risk factor for multiple neurodevelopmental and psychiatric disorders, including schizophrenia. However, the molecular and neurobiological mechanisms through which MIA imparts risk for these disorders remain poorly understood. A recently developed nonhuman primate model of exposure to the viral mimic poly:ICLC during pregnancy shows abnormal social and repetitive behaviors and elevated striatal dopamine, a molecular hallmark of human psychosis, providing an unprecedented opportunity for mechanistic dissection.Methods: We performed RNA-sequencing across four psychiatrically-relevant brain regions (prefrontal cortex, anterior cingulate, hippocampus, and primary visual cortex) from 3.5-4-year old male MIA-exposed and control offspring-an age comparable to mid adolescence in humans. Results:We identify 266 unique genes differentially expressed (DE) in at least one brain region with the greatest number observed in hippocampus. Co-expression networks identified region-specific alterations in synaptic signaling and oligodendrocytes. Across regions, we observed temporal and regional differences, but transcriptomic changes were largely similar across 1 st or 2 nd trimester MIA exposures, including for the top DE genes-PIWIL2 and MGARP. In addition to PIWIL2, several other known regulators of retrotransposition, as well as endogenous transposable elements were dysregulated in MIA offspring.Conclusions: Together, these results begin to elucidate the brain-level molecular mechanisms through which MIA may impart risk for psychiatric disease.

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Localization of nectin-2δ at perivascular astrocytic endfoot processes and degeneration of astrocytes and neurons in nectin-2 knockout mouse brain

Cited by 24 publications

References 51 publications

Localization of nectin‐2α at the boundary between the adjacent somata of the clustered cholinergic neurons and its regulatory role in the subcellular localization of the voltage‐gated A‐type K⁺ channel Kv4.2 in the medial habenula

Localization of nectin‐2α at the boundary between the adjacent somata of the clustered cholinergic neurons and its regulatory role in the subcellular localization of the voltage‐gated A‐type K⁺ channel Kv4.2 in the medial habenula

Aging‐dependent expression of synapse‐related proteins in the mouse brain

Alterations in retrotransposition, synaptic connectivity, and myelination implicated by transcriptomic changes following maternal immune activation in non-human primates

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Localization of nectin-2δ at perivascular astrocytic endfoot processes and degeneration of astrocytes and neurons in nectin-2 knockout mouse brain

Cited by 24 publications

References 51 publications

Localization of nectin‐2α at the boundary between the adjacent somata of the clustered cholinergic neurons and its regulatory role in the subcellular localization of the voltage‐gated A‐type K+ channel Kv4.2 in the medial habenula

Localization of nectin‐2α at the boundary between the adjacent somata of the clustered cholinergic neurons and its regulatory role in the subcellular localization of the voltage‐gated A‐type K+ channel Kv4.2 in the medial habenula

Aging‐dependent expression of synapse‐related proteins in the mouse brain

Alterations in retrotransposition, synaptic connectivity, and myelination implicated by transcriptomic changes following maternal immune activation in non-human primates

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Localization of nectin‐2α at the boundary between the adjacent somata of the clustered cholinergic neurons and its regulatory role in the subcellular localization of the voltage‐gated A‐type K⁺ channel Kv4.2 in the medial habenula

Localization of nectin‐2α at the boundary between the adjacent somata of the clustered cholinergic neurons and its regulatory role in the subcellular localization of the voltage‐gated A‐type K⁺ channel Kv4.2 in the medial habenula