The Interplay between Cytoskeleton and Calcium Dynamics

Martı́n-Romero, Francisco Javier; López-Guerrero, Aida M.; CarlosPascual-Caro,; Pozo‐Guisado, Eulalia

doi:10.5772/66862

Cited by 9 publications

(21 citation statements)

References 76 publications

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“…Remodeling of the actin cytoskeleton plays a role in determining cell shape and migration [ 39 ]. One of the key regulators of actin dynamics is Ca 2+ that acts through a variety of Ca 2+ -dependent regulatory mechanisms [ 8 , 9 ]. Since PMCAs are considered as important regulators of intracellular Ca 2+ concentration, we labeled A375 cells with Phalloidin-TRITC and studied the role of PMCA4b in F-actin organization with confocal laser scanning microscopy.…”

Section: Resultsmentioning

confidence: 99%

“…The calcium ion is considered as a modulator of actin dynamics, and a higher intracellular Ca 2+ concentration is found to promote cell migration [ 8 , 11 ]. Previously, we identified the PMCA4b Ca 2+ pump as a putative metastatic suppressor in BRAF mutant melanoma cells [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies suggested that cytoplasmic free Ca 2+ concentration plays a role in actin-based changes of cell polarity, chemotaxis, and motility [ 5 , 6 , 7 ]. In addition, Ca 2+ is involved in actin rearrangement, focal adhesion turnover, invadopodia, and lamellipodia formation during cell migration [ 8 , 9 ]. Cells maintain Ca 2+ homeostasis using a “molecular toolkit” that includes Ca 2+ channels to allow Ca 2+ to enter the cell and pumps or exchangers to remove excess Ca 2+ for proper cell functioning.…”

Section: Introductionmentioning

confidence: 99%

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The Plasma Membrane Ca2+ Pump PMCA4b Regulates Melanoma Cell Migration through Remodeling of the Actin Cytoskeleton

Naffa

Padányi

Ignácz

et al. 2021

Cancers

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We demonstrated that the plasma membrane Ca2+ ATPase PMCA4b inhibits migration and metastatic activity of BRAF mutant melanoma cells. Actin dynamics are essential for cells to move, invade and metastasize, therefore, we hypothesized that PMCA4b affected cell migration through remodeling of the actin cytoskeleton. We found that expression of PMCA4b in A375 BRAF mutant melanoma cells induced a profound change in cell shape, cell culture morphology, and displayed a polarized migratory character. Along with these changes the cells became more rounded with increased cell–cell connections, lamellipodia and stress fiber formation. Silencing PMCA4b in MCF-7 breast cancer cells had a similar effect, resulting in a dramatic loss of stress fibers. In addition, the PMCA4b expressing A375 cells maintained front-to-rear Ca2+ concentration gradient with the actin severing protein cofilin localizing to the lamellipodia, and preserved the integrity of the actin cytoskeleton from a destructive Ca2+ overload. We showed that both PMCA4b activity and trafficking were essential for the observed morphology and motility changes. In conclusion, our data suggest that PMCA4b plays a critical role in adopting front-to-rear polarity in a normally spindle-shaped cell type through F-actin rearrangement resulting in a less aggressive melanoma cell phenotype.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Plasma Membrane Ca2+ Pump PMCA4b Regulates Melanoma Cell Migration through Remodeling of the Actin Cytoskeleton

Naffa

Padányi

Ignácz

et al. 2021

Cancers

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“…It appears clear that coordinated interplay between different molecules is necessary to mediate the transient formation of ER-PM junctions (Grigoriev et al, 2008;Sharma et al, 2013;Maléth et al, 2014;Woo et al, 2016), but whether the integrity of cytoskeleton is needed for proper SOCE activation is not clear. Opposing data are present in literature, suggesting both inhibition (Oka et al, 2005;Smyth et al, 2007) or potentiation (Galán et al, 2011) of SOCE in the presence of MT-depolymerizing agents (Russa et al, 2009;Martin-Romero et al, 2017). To sort this out, we performed an in vivo approach in Drosophila melanogaster exploiting an endogenous means to manipulate MT dynamic instability.…”

Section: Discussionmentioning

confidence: 99%

Microtubules Stabilization by Mutant Spastin Affects ER Morphology and Ca2+ Handling

et al. 2019

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The endoplasmic reticulum (ER) extends as a network of interconnected tubules and sheet-like structures in eukaryotic cells. ER tubules dynamically change their morphology and position within the cells in response to physiological stimuli and these network rearrangements depend on the microtubule (MT) cytoskeleton. Store-operated calcium entry (SOCE) relies on the repositioning of ER tubules to form specific ER-plasma membrane junctions. Indeed, the tips of polymerizing MTs are supposed to provide the anchor for ER tubules to move toward the plasma membrane, however the precise role of the cytoskeleton during SOCE has not been conclusively clarified. Here we exploit an in vivo approach involving the manipulation of MT dynamics in Drosophila melanogaster by neuronal expression of a dominant-negative variant of the MT-severing protein spastin to induce MT hyper-stabilization. We show that MT stabilization alters ER morphology, favoring an enrichment in ER sheets at the expense of tubules. Stabilizing MTs has a negative impact on the process of SOCE and results in a reduced ER Ca 2+ content, affecting the flight ability of the flies. Restoring proper MT organization by administering the MT-destabilizing drug vinblastine, chronically or acutely, rescues ER morphology, SOCE and flight ability, indicating that MT dynamics impairment is responsible for all the phenotypes observed.

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“…To be efficient, cell migration requires tight spatiotemporal control of cellular signaling. Together with other molecules involved in the control of cell migration, calcium ion (Ca 2+ ) has emerged as a key modulator of cytoskeleton reorganization in migrating cells 1 . Ca 2+ signaling regulates cell migration in different aspects: the turnover of focal adhesions 2,3 , the contraction of actomyosin fibers (reviewed in 4 ), plasma membrane ruffling 5,6 , and the formation of podosomes 7 .…”

mentioning

confidence: 99%

RAC1-Dependent ORAI1 Translocation to the Leading Edge Supports Lamellipodia Formation and Directional Persistence

López-Guerrero

Espinosa-Bermejo

Sanchez-Lopez

et al. 2020

Sci Rep

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Tumor invasion requires efficient cell migration, which is achieved by the generation of persistent and polarized lamellipodia. The generation of lamellipodia is supported by actin dynamics at the leading edge where a complex of proteins known as the WAVE regulatory complex (WRC) promotes the required assembly of actin filaments to push the front of the cell ahead. By using an U2OS osteosarcoma cell line with high metastatic potential, proven by a xenotransplant in zebrafish larvae, we have studied the role of the plasma membrane Ca 2+ channel ORAI1 in this process. We have found that epidermal growth factor (EGF) triggered an enrichment of ORAI1 at the leading edge, where colocalized with cortactin (CTTN) and other members of the WRC, such as CYFIP1 and ARP2/3. ORAI1-CTTN co-precipitation was sensitive to the inhibition of the small GTPase RAC1, an upstream activator of the WRC. RAC1 potentiated ORAI1 translocation to the leading edge, increasing the availability of surface ORAI1 and increasing the plasma membrane ruffling. The role of ORAI1 at the leading edge was studied in genetically engineered U2OS cells lacking ORAI1 expression that helped us to prove the key role of this Ca 2+ channel on lamellipodia formation, lamellipodial persistence, and cell directness, which are required for tumor cell invasiveness in vivo.

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The Interplay between Cytoskeleton and Calcium Dynamics

Cited by 9 publications

References 76 publications

The Plasma Membrane Ca2+ Pump PMCA4b Regulates Melanoma Cell Migration through Remodeling of the Actin Cytoskeleton

The Plasma Membrane Ca2+ Pump PMCA4b Regulates Melanoma Cell Migration through Remodeling of the Actin Cytoskeleton

Microtubules Stabilization by Mutant Spastin Affects ER Morphology and Ca2+ Handling

RAC1-Dependent ORAI1 Translocation to the Leading Edge Supports Lamellipodia Formation and Directional Persistence

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