Galectin-8, cytokines, and the storm

Zick, Yehiel

doi:10.1042/bst20200677

Cited by 27 publications

(20 citation statements)

References 143 publications

(227 reference statements)

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“…Gal-8 has been shown to be a constituent of the ECM, functions as a pro-metastatic agent. It was suggested that it functions via enhanced cell adhesion properties 42 . The spreading of cells on a typical ECM protein, e.g., fibronectin, proceeds as a mix of protrusive activity and retraction 43 , 58 , 59 .…”

Section: Discussionmentioning

confidence: 99%

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A network of mixed actin polarity in the leading edge of spreading cells

Chung

Eibauer

et al. 2022

Commun Biol

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Physical interactions of cells with the underlying extracellular matrix (ECM) play key roles in multiple cellular processes. The actin cytoskeleton is a central driver and regulator of cellular dynamics, that produces membrane-protrusions such as lamellipodia and filopodia. Here, we examined actin organization in expanding lamellipodia during early stages of cell spreading. To gain insight into the 3D actin organization, we plated fibroblasts on galectin-8 coated EM grids, an ECM protein presents in disease states. We then combined cryo-electron tomography with advanced image processing tools for reconstructing the structure of F-actin in the lamellipodia. This approach enabled us to resolve the polarity and orientation of filaments, and the structure of the Arp2/3 complexes associated with F-actin branches. We show that F-actin in lamellipodial protrusions forms a dense network with three distinct sub-domains. One consists primarily of radial filaments, with their barbed ends pointing towards the membrane, the other is enriched with parallel filaments that run between the radial fibers, in addition to an intermediate sub-domain. Surprisingly, a minor, yet significant (~10%) population of actin filaments, are oriented with their barbed-ends towards the cell center. Our results provide structural insights into F-actin assembly and dynamic reorganization in the leading edge of spreading cells.

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Section: Discussionmentioning

confidence: 99%

“…Galectins interact with the cell-surface receptors that impact cell signaling and adhesion to the ECM. These interactions facilitate cell migration in a variety of model systems such as glioblastoma 40 , keratinocyte, B16 melanoma and act through the Rho/Rac pathway in different cellular systems 41 , 42 .…”

Section: Introductionmentioning

confidence: 99%

A network of mixed actin polarity in the leading edge of spreading cells

Chung

Eibauer

et al. 2022

Commun Biol

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“…Gal-8 has shown to be a constituent of the ECM, functions as a pro-metastatic agent. It was suggested that it functions via enhanced cell adhesion properties 53 .…”

Section: Discussionmentioning

confidence: 99%

A network of mixed actin polarity in the leading edge of spreading cells

Chung

Eibauer

et al. 2022

Preprint

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Physical interactions of cells with the underlying extracellular matrix (ECM) play key roles in multiple cellular processes, such as tissue morphogenesis, cell motility, wound healing, cancer invasion and metastasis. The actin cytoskeletal network is a central driver and regulator of cellular dynamics, that produces membrane protrusions such as lamellipodia and filopodia. In this study, we examined actin organization in the expanding lamellipodia during the early stages of cell spreading. To gain insight into the 3D actin organization, at a molecular resolution, we plated cultured fibroblasts on galectin-8 coated EM grids, an ECM protein presents in disease states. We then combined cryo-electron tomography (cryo-ET) with advanced image processing tools for reconstructing the structure of F-actin in the lamellipodia. This approach enabled us to resolve the polarity and orientation of the filaments, and the structure of the Arp2/3 complexes associated with F-actin branches. We show here that F-actin in lamellipodial protrusions forms a dense network with three distinct sub-domains. One consists primarily of radial filaments, with their barbed ends pointing towards the membrane, the other is enriched with parallel filaments that run between the radial fibers, in addition to an intermediate sub-domain. Surprisingly, a minor, yet significant (~10%) population of actin filaments, are oriented with their barbed ends towards the cell center. Our results provide novel structural insights into F-actin assembly and dynamic reorganization in the leading edge of spreading cells.

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“…Galectin-8 has also been shown to trigger cytokine expression and release in different cell types (For a recent review, see [ 102 ]). For example, galectin-8 was described to induce the proliferation of resting T cells [ 103 , 104 ] which was accompanied by increased expression of IL-2, IFN-γ, and IL-4 [ 104 ].…”

Section: Indirect Relationship Between Galectins and Cytokinesmentioning

confidence: 99%

“…In line with this, galectin-8 knockout mice displayed a systemic reduction of expression of, e.g., IL-6, TNF-α, and MCP-1 [ 108 ]. Recently, it was hypothesized that galectin-8 could also enhance the development of the cytokine storm observed in COVID-19 patients [ 102 ].…”

Section: Indirect Relationship Between Galectins and Cytokinesmentioning

confidence: 99%

Galectokines: The Promiscuous Relationship between Galectins and Cytokines

et al. 2022

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Galectins, a family of glycan-binding proteins, are well-known for their role in shaping the immune microenvironment. They can directly affect the activity and survival of different immune cell subtypes. Recent evidence suggests that galectins also indirectly affect the immune response by binding to members of another immunoregulatory protein family, i.e., cytokines. Such galectin-cytokine heterodimers, here referred to as galectokines, add a new layer of complexity to the regulation of immune homeostasis. Here, we summarize the current knowledge with regard to galectokine formation and function. We describe the known and potential mechanisms by which galectokines can help to shape the immune microenvironment. Finally, the outstanding questions and challenges for future research regarding the role of galectokines in immunomodulation are discussed.

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Galectin-8, cytokines, and the storm

Cited by 27 publications

References 143 publications

A network of mixed actin polarity in the leading edge of spreading cells

A network of mixed actin polarity in the leading edge of spreading cells

A network of mixed actin polarity in the leading edge of spreading cells

Galectokines: The Promiscuous Relationship between Galectins and Cytokines

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