Lack of Paxillin phosphorylation promotes single-cell migration in vivo

Xue, Qian; Varady, Sophia R S; Waddell, Trinity Q Alaka'i; Roman, Mackenzie R.; Carrington, James; Roh-Johnson, Minna

doi:10.1083/jcb.202206078

Cited by 10 publications

(19 citation statements)

References 101 publications

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“…1d). In agreement with this result, FRAP experiments in MEF cells and zebrafish macrophages showed characteristic turnover times of less than one minute for fluorescently labeled paxillin in focal adhesions and invadosomes [46,87,89,90]. Excessive IQGAP1 accumulation correlated with slower paxillin turnover, elongation of focal adhesions and impaired cell migration [46], suggesting that timely removal of IQGAP1 is important for the dynamics of focal adhesion.…”

Section: Iqgc Participates In a Rapa-stimulated Adhesion Pathwaysupporting

confidence: 73%

The IQGAP-related RasGAP IqgC regulates cell-substratum adhesion in Dictyostelium discoideum

Mijanovic,

Putar,

Mimica

et al. 2024

Preprint

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Proper adhesion of cells to their environment is essential for the normal functioning of single cells and multicellular organisms. To attach to the extracellular matrix (ECM), mammalian cells form integrin adhesion complexes consisting of many proteins that together link the ECM and the actin cytoskeleton. Similar to mammalian cells, the amoeboid cells of the protist Dictyostelium discoideum also use multiprotein adhesion complexes to control their attachment to the underlying surface. However, the exact composition of the multiprotein complexes and the signaling pathways involved in the regulation of adhesion in D. discoideum have not yet been elucidated. Here we show that the IQGAP-related protein IqgC is important for normal attachment of D. discoideum cells to the substratum. Mutant iqgC-null cells have impaired adhesion, whereas overexpression of IqgC promotes directional migration. A RasGAP C-terminal (RGCt) domain of IqgC is sufficient for its localization in the ventral adhesion focal complexes, while RasGAP activity of a GAP-related domain (GRD) is additionally required for the proper function of IqgC in adhesion. We identify the small GTPase RapA as a novel direct IqgC interactor and show that IqgC participates in a RapA-regulated signaling pathway targeting the adhesion complexes that include talin A, myosin VII and paxillin B. Based on our results, we propose that IqgC is a positive regulator of adhesion, responsible for the strengthening of ventral adhesion structures and for the temporal control of their subsequent degradation.

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Section: Iqgc Participates In a Rapa-stimulated Adhesion Pathwaysupporting

confidence: 73%

The IQGAP-related RasGAP IqgC regulates cell-substratum adhesion in Dictyostelium discoideum

Mijanovic,

Putar,

Mimica

et al. 2024

Preprint

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“…The work demonstrating Dictyostelium's use of homologues of core focal adhesion components for adhesion-based migration, in conjunction with its amoeboid migration-like characteristics, make it an ideal system for investigating novel aspects of focal adhesion function and regulation during cell migration in non-mesenchymal contexts such as amoeboid cells. Furthermore, the lack of putative homologues of certain core focal adhesion components makes Dictyostelium an interesting model to investigate how focal adhesions are assembled and regulated for efficient migration in conditions where key components are missing, as this can give insight into differential modes of focal adhesion regulation and assembly relevant to physiological environments (Caillier et al, 2023;Xue et al, 2023;Zhang et al, 2023). We sought to understand how Dictyostelium form and regulate focal adhesions during single cell migration.…”

Section: Introductionmentioning

confidence: 99%

Reduced PaxillinB localization to cell-substrate adhesions promotes cell migration inDictyostelium

Morales,

Redfearn,

Titus

et al. 2024

Preprint

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Many cells adhere to extracellular matrix for efficient cell migration. This adhesion is mediated by focal adhesions, a protein complex linking the extracellular matrix to the intracellular cytoskeleton. Focal adhesions have been studied extensively in mesenchymal cells, but recent research in physiological contexts and amoeboid cells suggest focal adhesion regulation differs from the mesenchymal focal adhesion paradigm. We used Dictyostelium discoideum to uncover new mechanisms of focal adhesion regulation, as Dictyostelium are amoeboid cells that form focal adhesion-like structures for migration. We show that PaxillinB, the Dictyostelium homologue of Paxillin, localizes to dynamic focal adhesion-like structures during Dictyostelium migration. Unexpectedly, reduced PaxillinB recruitment to these structures increases Dictyostelium cell migration. Quantitative analysis of focal adhesion size and dynamics show that lack of PaxillinB recruitment to focal adhesions does not alter focal adhesion size, but rather increases focal adhesion turnover. These findings are in direct contrast to Paxillin function at focal adhesions during mesenchymal migration, challenging the established focal adhesion model.

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“…[ 4 ] As main mediators of force transmission, proteins such as vinculin, talin, paxillin, and focal adhesion kinase have been identified. [ 5–8 ]…”

Section: Introductionmentioning

confidence: 99%

“…[4] As main mediators of force transmission, proteins such as vinculin, talin, paxillin, and focal adhesion kinase have been identified. [5][6][7][8] A lot of progress has been made in recent years to investigate the effect of mechanical stretching on single cells [9,10] and on multicellular assemblies, [11,12] including 3D stretching. [13,14] Typically, such forces are applied to cell sheets on or in elastic materials, which lack both micrometer precision and structural control of cell positioning at the micrometer scale, which would be highly valuable to mimic specific human tissue environments.…”

Section: Introductionmentioning

confidence: 99%

Two‐Photon Laser Printing to Mechanically Stimulate Multicellular Systems in 3D

Colombo,

Taale,

Taheri

et al. 2024

Adv Funct Materials

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Biological activities take place in 3D environments, where cells interact in various directions in a defined, often microstructured, space. A sub‐millimeter‐sized stretching device is developed to mechanically stimulate a structurally restricted, soft multicellular microenvironment to investigate the effect of defined cyclic mechanical forces on a multicellular system. It consists of a multi‐material 3D microstructure made of Polydimethylsiloxane (PDMS) and gelatine‐based hydrogel, which is printed using the 2‐photon polymerization (2PP) method. The printed structures are first characterized microscopically and mechanically to study the effect of different printing parameters. Using 2PP, organotypic cell cultures are then directly printed into the hydrogel structures to create true 3D cell culture systems. These systems are mechanically stimulated with a cantilever by indenting at defined positions. The cells in the 3D organotypic cell culture change morphology and actin orientation when exposed to cyclic mechanical stretch, even within short timescales of 30 min. As proof of concept, a Medaka retinal organoid is encapsulated in the same structure to demonstrate that even preformed organoids can be stimulated by this method. The results highlight the capability of 2PP for manufacturing multifunctional soft devices to mechanically control multicellular systems at micrometer resolution and thus mimic mechanical stresses as they occur in vivo.

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Lack of Paxillin phosphorylation promotes single-cell migration in vivo

Cited by 10 publications

References 101 publications

The IQGAP-related RasGAP IqgC regulates cell-substratum adhesion in Dictyostelium discoideum

The IQGAP-related RasGAP IqgC regulates cell-substratum adhesion in Dictyostelium discoideum

Reduced PaxillinB localization to cell-substrate adhesions promotes cell migration inDictyostelium

Two‐Photon Laser Printing to Mechanically Stimulate Multicellular Systems in 3D

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