Calreticulin and focal-contact-dependent adhesion

Villagomez, Maria VillagomezM.; Szabó, Éva; Podcheko, Alexey; Feng, Tianshu; Papp, Sylvia; Opas, Michał

doi:10.1139/o09-016

Cited by 23 publications

(15 citation statements)

References 121 publications

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“…Calreticulin targets focal adhesion‐dependent adhesion [16], such that cells with reduced calreticulin expression also have reduced cell‐substratum adhesion via focal adhesions and are less spread [16]. Therefore, we immunolocalized focal adhesion proteins and fibronectin in the cellular outgrowths from EBs.…”

Section: Resultsmentioning

confidence: 99%

“…Numerous studies have indicated that alterations in calreticulin levels affect both cell shape and adhesion in a variety of cell types [7–14], including stem cells [15]. Cells that are either underexpressing or lacking calreticulin have impaired cell adhesion, whereas overexpression of calreticulin increases adherens‐type adhesion in both cell‐substratum (i.e., focal adhesions) and cell‐cell (i.e., zonulae adherens) varieties [16]. Because calreticulin has not been detected in adherens‐type adhesions, it seems that the adhesion‐related effects of differential calreticulin expression originate from within the ER lumen.…”

Section: Introductionmentioning

confidence: 99%

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Cell Adhesion and Spreading Affect Adipogenesis from Embryonic Stem Cells: The Role of Calreticulin

et al. 2009

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Calreticulin is an endoplasmic reticulum-resident multifunctional protein, which has been shown to influence numerous cellular processes, including cell adhesion. In this study, we characterized the adhesive properties of embryonic stem cells (ESCs) lacking calreticulin and showed that adipogenesis from ESCs is directly and reciprocally controlled by the adhesive status of a cell, which in turn is modulated by calreticulin. Calreticulin-deficient ESCs are not only highly adipogenic but also show elevated calmodulin/CaMKII signaling and poor adhesiveness compared with the wild-type ESCs. Calreticulin deficiency leads to a disorganized cytoskeleton and low levels of focal adhesionrelated proteins, such as vinculin, paxillin, and phosphorylated focal adhesion kinase, which cause limited focal adhesion formation and limited fibronectin deposition. Moreover, differentiation on nonadhesive substrata, which hinder cell spreading, promoted adipogenesis in the wildtype ESCs that normally have low adipogenic potential, causing a decrease in focal adhesion protein expression and an increase in calmodulin/CaMKII signaling. In contrast, inhibition of CaMKII effectively increased focal adhesion protein levels and inhibited adipogenesis in calreticulin-deficient ESCs, causing them to behave like the low adipogenic, wild-type ESCs. Thus, the adipogenic potential of ESCs is proportional to their calmodulin/ CaMKII activity but is inversely related to their focal adhesion protein levels and degree of adhesiveness/spreading.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cell Adhesion and Spreading Affect Adipogenesis from Embryonic Stem Cells: The Role of Calreticulin

et al. 2009

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“…These cells also exhibit increased expression of the adipogenic transcription factors, PPARγ2 and C/EBPα in EBs at day 20 of differentiation in comparison to the WT ES cells. Importantly, like many other cell types deficient in calreticulin [29], calreticulinnull (G45crt -/-) ES cells show dramatically reduced extent of cell spreading and adhesiveness in comparison to WT cells [12,17].…”

Section: Resultsmentioning

confidence: 99%

Cytoskeletal Disassembly and Cell Rounding Promotes Adipogenesis from ES Cells

Feng

Szabó

Dziak

et al. 2010

Stem Cell Rev and Rep

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Biomechanical signals such as cell shape and spreading play an important role in controlling stem cell commitment. Cell shape, adhesion and spreading are also affected by calreticulin, a multifunctional calcium-binding protein, which influences several cellular processes, including adipogenesis. Here we show that cytoskeletal disruption in mouse embryonic stem cells using cytochalasin D or nocodazole promotes adipogenesis. While cytochalasin D disrupts stress fibres and inhibits focal adhesion formation, nocodazole depolymerises microtubules and promotes focal adhesion formation. Furthermore, cytochalasin D increases the levels of both total and activated calcium/calmodulin-dependent protein kinase II, whereas nocodazole decreases it. Nevertheless, both treatments significantly increase the adipogenic potential of embryonic stem cells in vitro. Both cytochalasin D and nocodazole exposure caused cell rounding suggesting that it is cell shape that causes the switch towards the adipogenic programme. Calreticulin-containing embryonic stem cells, under baseline conditions, show low adipogenic potential, have low activity of signalling via calcium/calmodulin-dependent protein kinase II and display normal adhesive properties and cellular spreading in comparison to the highly adipogenic but poorly spread calreticulin-deficient ES cells. We conclude that forced cell rounding via cytoskeletal disruption overrides the effects of calreticulin, an ER chaperone, thus negatively regulating adipogenesis via focal adhesion-mediated cell spreading.

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“…Thus, endocannabinoids might assist in the formation of focal adhesions and rearrangement of the actin cytoskeleton in SFs. One important second messenger that affects integrin avidity and affinity directly and indirectly via adaptor proteins is calcium (36).…”

Section: Discussionmentioning

confidence: 99%

Cortisol‐mediated adhesion of synovial fibroblasts is dependent on the degradation of anandamide and activation of the endocannabinoid system

Lowin

Zhu

Dettmer-Wilde

et al. 2012

Arthritis & Rheumatism

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Objective. In rheumatoid arthritis (RA) synovial fluid, levels of the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol are elevated. Since synovial fibroblasts (SFs) possess all of the enzymes necessary for endocannabinoid synthesis, it is likely that these cells contribute significantly to elevated endocannabinoid levels. While glucocorticoids initiate endocannabinoid synthesis in neurons, this study was undertaken to test whether cortisol also regulates endocannabinoid levels in mesenchymal cells such as SFs, and whether this interferes with integrin-mediated adhesion.Methods. Adhesion was determined in 1-minute intervals over 60 minutes using an xCELLigence system. Slopes from individual treatment groups were averaged and compared to the control. Fatty acid amide hydrolase (FAAH) and cyclooxygenase 2 (COX-2) were detected by immunocytochemistry, and AEA was detected by mass spectrometry. Conclusion. Our findings indicate that glucocorticoid-induced adhesion is dependent on CB 1 / CB 2 /TRPV-1 activation. Since AEA is produced in SFs, this endocannabinoid is the most likely candidate to mediate these effects. Since AEA levels are regulated by COX-2 and FAAH, inhibition of both enzymes along with low-dose glucocorticoids may provide a therapeutic option to maximally boost the endocannabinoid system in RA, with possible beneficial effects. Results. Cortisol increased the adhesion of RASFs and osteoarthritis

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Calreticulin and focal-contact-dependent adhesion

Cited by 23 publications

References 121 publications

Cell Adhesion and Spreading Affect Adipogenesis from Embryonic Stem Cells: The Role of Calreticulin

Cell Adhesion and Spreading Affect Adipogenesis from Embryonic Stem Cells: The Role of Calreticulin

Cytoskeletal Disassembly and Cell Rounding Promotes Adipogenesis from ES Cells

Cortisol‐mediated adhesion of synovial fibroblasts is dependent on the degradation of anandamide and activation of the endocannabinoid system

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