Intracellular Ca2+ Increases and Connexin 43 Hemichannel Opening Are Necessary but Not Sufficient for Thy-1-Induced Astrocyte Migration

Lagos-Cabré, Raúl; Brenet, Marianne; Díaz, Jorge; Pérez, Ramón; Pérez, Leonardo A.; Herrera-Molina, Rodrigo; Quest, Andrew F. G.; Leyton, Lisette

doi:10.3390/ijms19082179

Cited by 27 publications

(33 citation statements)

References 37 publications

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“…Higher adhesion frequencies of Syndecan-4 with Thy-1-Fc wild type [Thy-1(RLD)-Fc] compared to the control conditions with TRAIL-R2-Fc receptor (TRAIL-R2-Fc) or beads without proteins (Buffer) were observed ( Figure 1B ). TRAIL-R2-Fc is an Fc-tagged protein that serves as a negative control in all our functional assays ( Maldonado et al, 2017 ; Lagos-Cabré et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

Application of Force to a Syndecan-4 Containing Complex With Thy-1–αVβ3 Integrin Accelerates Neurite Retraction

Burgos‐Bravo

Martínez-Meza

Quest

et al. 2020

Front. Mol. Biosci.

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Inflammation contributes to the genesis and progression of chronic diseases, such as cancer and neurodegeneration. Upregulation of integrins in astrocytes during inflammation induces neurite retraction by binding to the neuronal protein Thy-1, also known as CD90. Additionally, Thy-1 alters astrocyte contractility and movement by binding to the mechano-sensors α V β 3 integrin and Syndecan-4. However, the contribution of Syndecan-4 to neurite shortening following Thy-1–α V β 3 integrin interaction remains unknown. To further characterize the contribution of Syndecan-4 in Thy-1-dependent neurite outgrowth inhibition and neurite retraction, cell-based assays under pro-inflammatory conditions were performed. In addition, using Optical Tweezers, we studied single-molecule binding properties between these proteins, and their mechanical responses. Syndecan-4 increased the lifetime of Thy-1–α V β 3 integrin binding by interacting directly with Thy-1 and forming a ternary complex (Thy-1–α V β 3 integrin + Syndecan-4). Under in vitro -generated pro-inflammatory conditions, Syndecan-4 accelerated the effect of integrin–engaged Thy-1 by forming this ternary complex, leading to faster neurite retraction and the inhibition of neurite outgrowth. Thus, Syndecan-4 controls neurite cytoskeleton contractility by modulating α V β 3 integrin mechano-receptor function. These results suggest that mechano-transduction, cell-matrix and cell-cell interactions are likely critical events in inflammation-related disease development.

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Section: Resultsmentioning

confidence: 99%

Application of Force to a Syndecan-4 Containing Complex With Thy-1–αVβ3 Integrin Accelerates Neurite Retraction

Burgos‐Bravo

Martínez-Meza

Quest

et al. 2020

Front. Mol. Biosci.

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“…Importantly, this finding led to the idea that Cx43 played a relevant role in regulating astrocytic mobility. Since then, several studies have reported that Cxs affect astrocyte migration (Homkajorn et al, 2010;Kotini and Mayor, 2015;Lagos-Cabre, 2018).…”

Section: Introductionmentioning

confidence: 99%

Connexins in Astrocyte Migration

et al. 2020

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Astrocytes have long been considered the supportive cells of the central nervous system, but during the last decades, they have gained much more attention because of their active participation in the modulation of neuronal function. For example, after brain damage, astrocytes become reactive and undergo characteristic morphological and molecular changes, such as hypertrophy and increase in the expression of glial fibrillary acidic protein (GFAP), in a process known as astrogliosis. After severe damage, astrocytes migrate to the lesion site and proliferate, which leads to the formation of a glial scar. At this scarforming stage, astrocytes secrete many factors, such as extracellular matrix proteins, cytokines, growth factors and chondroitin sulfate proteoglycans, stop migrating, and the process is irreversible. Although reactive gliosis is a normal physiological response that can protect brain cells from further damage, it also has detrimental effects on neuronal survival, by creating a hostile and non-permissive environment for axonal repair. The transformation of astrocytes from reactive to scar-forming astrocytes highlights migration as a relevant regulator of glial scar formation, and further emphasizes the importance of efficient communication between astrocytes in order to orchestrate cell migration. The coordination between astrocytes occurs mainly through Connexin (Cx) channels, in the form of direct cell-cell contact (gap junctions, GJs) or contact between the extracellular matrix and the astrocytes (hemichannels, HCs). Reactive astrocytes increase the expression levels of several proteins involved in astrocyte migration, such as a v b 3 Integrin, Syndecan-4 proteoglycan, the purinergic receptor P2X7, Pannexin1, and Cx43 HCs. Evidence has indicated that Cx43 HCs play a role in regulating astrocyte migration through the release of small molecules to the extracellular space, which then activate receptors in the same or adjacent cells to continue the signaling cascades required for astrocyte migration. In this review, we describe the communication of astrocytes through Cxs, the role of Cxs in inflammation and astrocyte migration, and discuss the molecular mechanisms that regulate Cx43 HCs, which may provide a therapeutic window of opportunity to control astrogliosis and the progression of neurodegenerative diseases.

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“…5,6 CaSR increases the concentration of intracellular calcium ([Ca 2+ ] i ) by up-regulation of the IP3-PLC pathway. 7 Ca 2+ promotes cell proliferation by activating ERK and PI3K-Akt pathways. 7,8 Our current study showed that CaSR was ex-…”

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confidence: 99%

“…7 Ca 2+ promotes cell proliferation by activating ERK and PI3K-Akt pathways. 7,8 Our current study showed that CaSR was ex-…”

mentioning

confidence: 99%

Calcium‐sensing receptor activating ERK1/2 and PI3K‐Akt pathways to induce the proliferation of osteosarcoma cells

Zhao

Zhang

Zheng

et al. 2019

Clin Exp Pharma Physio

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Our results showed that the expression of calcium-sensing receptor (CaSR) and the concentration of intracellular calcium were enhanced in the osteosarcoma cells MG-63 compared with in the normal osteoblasts hFOB1.19. GdCl 3 (CaSR agonist) significantly increased the proliferation rate of MG-63 cells, the expression of PCNA and Cyclin D1 and decreased the expression of p21 Cip/WAF-1 . The effect of NPS2390 (CaSR antagonist) on the above indicators was opposite to GdCl 3 . In addition, GdCl 3 up-regulated the phosphorylation of ERK1/2, PI3K and Akt and the proliferation rate of MG-63 cells. However, these effects of GdCl 3 were cancelled by LY294002 (a PI3K inhibitor) or PD98059 (an ERK1/2 inhibitor). Our results demonstrate that activation of CaSR promotes osteosarcoma cell multiplication by up-regulating ERK1/2 and PI3K-Akt pathways. K E Y W O R D Scalcium-sensing receptor, osteosarcoma cells, proliferation, signalling pathway How to cite this article: Zhao W, Zhang Z, Zheng L, et al.Calcium-sensing receptor activating ERK1/2 and PI3K-Akt pathways to induce the proliferation of osteosarcoma cells.

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Intracellular Ca2+ Increases and Connexin 43 Hemichannel Opening Are Necessary but Not Sufficient for Thy-1-Induced Astrocyte Migration

Cited by 27 publications

References 37 publications

Application of Force to a Syndecan-4 Containing Complex With Thy-1–αVβ3 Integrin Accelerates Neurite Retraction

Application of Force to a Syndecan-4 Containing Complex With Thy-1–αVβ3 Integrin Accelerates Neurite Retraction

Connexins in Astrocyte Migration

Calcium‐sensing receptor activating ERK1/2 and PI3K‐Akt pathways to induce the proliferation of osteosarcoma cells

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