Classical cadherins control nucleus and centrosome position and cell polarity

Dupin, Isabelle; Camand, Emeline; Etienne-Manneville, Sandrine

doi:10.1083/jcb.200812034

Cited by 169 publications

(182 citation statements)

References 26 publications

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“…N-cadherin in cultured astrocytes is known to regulate cell polarity, the essential determinant of the cell morphology and direction of migration (23,31). In line with this notion, aNcadKO astrocytes demonstrated defects in cell migration and morphological change after injury (Fig.…”

Section: N-cadherin Regulates Reactive Astrogliosis and Neuroprotectionsupporting

confidence: 67%

Calcium-dependent N-cadherin up-regulation mediates reactive astrogliosis and neuroprotection after brain injury

Kanemaru¹,

Kubota²,

Sekiya³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

132

108

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Brain injury induces phenotypic changes in astrocytes, known as reactive astrogliosis, which may influence neuronal survival. Here we show that brain injury induces inositol 1,4,5-trisphosphate (IP 3 )-dependent Ca 2+ signaling in astrocytes, and that the Ca 2+ signaling is required for astrogliosis. We found that type 2 IP 3 receptor knockout (IP 3 R2KO) mice deficient in astrocytic Ca 2+ signaling have impaired reactive astrogliosis and increased injuryassociated neuronal death. We identified N-cadherin and pumilio 2 (Pum2) as downstream signaling molecules, and found that brain injury induces up-regulation of N-cadherin around the injured site. This effect is mediated by Ca 2+ -dependent down-regulation of Pum2, which in turn attenuates Pum2-dependent translational repression of N-cadherin. Furthermore, we show that astrocyte-specific knockout of N-cadherin results in impairment of astrogliosis and neuroprotection. Thus, astrocytic Ca 2+ signaling and the downstream function of N-cadherin play indispensable roles in the cellular responses to brain injury. These findings define a previously unreported signaling axis required for reactive astrogliosis and neuroprotection following brain injury.calcium signal | reactive astrocyte | translational repressor | stab wound A strocytes, a major type of glial cell in the brain, play essential roles not only in physiological functions, such as synaptic plasticity and hemodynamic responses (1), but also in pathophysiological conditions, such as trauma, infection, ischemia, epileptic seizures and stroke. In response to brain injury, astrocytes undergo characteristic phenotypic changes known as reactive astrogliosis, which can exert both beneficial and detrimental effects on surrounding neurons (2-4). Despite the importance of this process, the molecular mechanisms governing astrogliosis and the role of reactive astrocytes require further clarification.Injury to the brain mobilizes astrocyte-reactivating factors, including ATP, endothelin 1 (ET1), glutamate, and inflammatory cytokines, as well as mechanical stress. These factors have been shown to evoke astrocytic Ca 2+ signals not only in culture, but also in acute brain slice preparations and in the brains of live animals (5-7). These findings raise the possibility that injury to the brain evokes astrocytic Ca 2+ signals, which in turn regulate reactive astrogliosis. However, injury-induced Ca 2+ signaling in astrocytes heretofore had not been observed in vivo, and the role of Ca 2+ signaling in pathophysiological processes after brain injury was not established.In this study, we investigated the involvement of astrocytic Ca 2+ signals and underlying molecular mechanisms in reactive astrogliosis and neuroprotection after traumatic brain injury. We found that neocortical injury evokes astrocytic Ca 2+ signals, which are required for reactive astrogliosis and neuronal protection. We identified N-cadherin and pumilio 2 (Pum2) as molecules acting downstream of astrocytic Ca 2+ signals. Around the injury site, N-cadherin is u...

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Section: N-cadherin Regulates Reactive Astrogliosis and Neuroprotectionsupporting

confidence: 67%

Calcium-dependent N-cadherin up-regulation mediates reactive astrogliosis and neuroprotection after brain injury

Kanemaru¹,

Kubota²,

Sekiya³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

132

108

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“…In the absence of p120catenin, this interaction promotes the proteasome-dependent degradation of cadherin [56]. However, in some cell types, such as astrocytes [57] and neurons [58], the expression level of cadherin is not so much impaired by p120catenin downregulation. This may reflect the fact that the two internalization motifs are absent in N-cadherin.…”

Section: Membrane-associated P120catenin and The Regulation Of Adherementioning

confidence: 99%

p120catenin alteration in cancer and its role in tumour invasion

Péglion

Etienne-Manneville

2013

Phil. Trans. R. Soc. B

Self Cite

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Since its discovery in 1989 as a substrate of the Src oncogene, p120catenin has been revealed as an important player in cancer initiation and tumour dissemination. p120catenin regulates a wide range of cellular processes such as cell–cell adhesion, cell polarity and cell proliferation and plays a pivotal role in morphogenesis, inflammation and innate immunity. The pleiotropic effects of p120catenin rely on its interactions with numerous partners such as classical cadherins at the plasma membrane, Rho-GTPases and microtubules in the cytosol and transcriptional modulators in the nucleus. Alterations of p120catenin in cancer not only concern its expression level but also its intracellular localization and can lead to both pro-invasive and anti-invasive effects. This review focuses on the p120catenin-mediated pathways involved in cell migration and invasion and discusses the potential consequences of major cancer-related p120catenin alterations with respect to tumour spread.

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“…In this latter preparation, glial cells are attached to each other at the border of the scratch. It was demonstrated previously that cultured migrating astrocytes establish lateral junctions containing N-cadherin that regulate cell orientation in the direction of the free cell edge [41]. Since nucleotides induce the expression of N-cadherin in cultured astrocytes [42] as well as in transformed cells [43], one Cell migration entails activation of a variety of molecular and cellular events that converge in morphological changes and cell displacement.…”

Section: Discussionmentioning

confidence: 99%

Involvement of nucleotides in glial growth following scratch injury in avian retinal cell monolayer cultures

Silva

França

Ornelas

et al. 2015

Purinergic Signalling

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When retinal cell cultures were mechanically scratched, cell growth over the empty area was observed. Only dividing and migrating, 2 M6-positive glial cells were detected. Incubation of cultures with apyrase (APY), suramin, or Reactive Blue 2 (RB-2), but not MRS 2179, significantly attenuated the growth of glial cells, suggesting that nucleotide receptors other than P2Y 1 are involved in the growth of glial cells. UTPγS but not ADPβS antagonized apyrase-induced growth inhibition in scratched cultures, suggesting the participation of UTP-sensitive receptors. No decrease in proliferating cell nuclear antigen (PCNA + ) cells was observed at the border of the scratch in apyrase-treated cultures, suggesting that glial proliferation was not affected. In apyrase-treated cultures, glial cytoplasm protrusions were smaller and unstable. Actin filaments were less organized and alfa-tubulinlabeled microtubules were mainly parallel to scratch. In contrast to control cultures, very few vinculin-labeled adhesion sites could be noticed in these cultures. Increased Akt and ERK phosphorylation was observed in UTP-treated cultures, effect that was inhibited by SRC inhibitor 1 and PI3K blocker LY294002. These inhibitors and the FAK inhibitor PF573228 also decreased glial growth over the scratch, suggesting participation of SRC, PI3K, and FAK in UTP-induced growth of glial cells in scratched cultures. RB-2 decreased dissociated glial cell attachment to fibronectin-coated dishes and migration through transwell membranes, suggesting that nucleotides regulated adhesion and migration of glial cells. In conclusion, mechanical scratch of retinal cell cultures induces growth of glial cells over the empty area through a mechanism that is dependent on activation of UTP-sensitive receptors, SRC, PI3K, and FAK.

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Classical cadherins control nucleus and centrosome position and cell polarity

Cited by 169 publications

References 26 publications

Calcium-dependent N-cadherin up-regulation mediates reactive astrogliosis and neuroprotection after brain injury

Calcium-dependent N-cadherin up-regulation mediates reactive astrogliosis and neuroprotection after brain injury

p120catenin alteration in cancer and its role in tumour invasion

Involvement of nucleotides in glial growth following scratch injury in avian retinal cell monolayer cultures

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