Galectin multimerization and lattice formation are regulated by linker region structure

Earl, L. A.; Bi, Shirley Z; Baum, L. G.

doi:10.1093/glycob/cwr011

Cited by 6 publications

(7 citation statements)

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“…Linear oligomeric ligands most effectively promote clustering of Con A, and the shape of the ligands is an important factor for determining the rate of oligomerization and density of Con A in clusters (54). Furthermore, properties of the linkers between the saccharides, such as flexibility and length, also affect oligomerization (30,39). These multivalent saccharide-lectin interactions share many parallels with the multivalent protein-protein interactions described later in this review.…”

Section: Carbohydrate-lectin Interactions In Receptor Oligomerizationmentioning

confidence: 82%

Regulation of Transmembrane Signaling by Phase Separation

Case

Ditlev

Rosen

2019

Annu. Rev. Biophys.

253

209

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Cell surface transmembrane receptors often form nanometer- to micrometer-scale clusters to initiate signal transduction in response to environmental cues. Extracellular ligand oligomerization, domain-domain interactions, and binding to multivalent proteins all contribute to cluster formation. Here we review the current understanding of mechanisms driving cluster formation in a series of representative receptor systems: glycosylated receptors, immune receptors, cell adhesion receptors, Wnt receptors, and receptor tyrosine kinases. We suggest that these clusters share properties of systems that undergo liquid–liquid phase separation and could be investigated in this light.

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Section: Carbohydrate-lectin Interactions In Receptor Oligomerizationmentioning

confidence: 82%

Regulation of Transmembrane Signaling by Phase Separation

Case

Ditlev

Rosen

2019

Annu. Rev. Biophys.

253

209

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“…Importantly, the amount of galectin-9 required for these effects may be relatively modest, as we observed effects on T-cell migrations at nanomolar concentrations of galectin-9 (Fig. 2); the potency of galectin-9 may result from the ability of this tandem repeat galectin to form multivalent oligomers (41). That galectin-9 promotes Th2 cell migration while killing Th1 cells suggests that galectin-9 expression will be of particular significance in disease mediated by Th2-type immune responses, such as asthma (23); galectin-9 expression is increased in lungs of mice in a model of allergic airway disease, and galectin-9 is also a chemokine for eosinophils (27,42).…”

Section: Discussionmentioning

confidence: 93%

Galectin-9 binding to cell surface protein disulfide isomerase regulates the redox environment to enhance T-cell migration and HIV entry

Bi¹,

Hong

Lee

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

211

215

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Interaction of cell surface glycoproteins with endogenous lectins on the cell surface regulates formation and maintenance of plasma membrane domains, clusters signaling complexes, and controls the residency time of glycoproteins on the plasma membrane. Galectin-9 is a soluble, secreted lectin that binds to glycoprotein receptors to form galectin-glycoprotein lattices on the cell surface. Whereas galectin-9 binding to specific glycoprotein receptors induces death of CD4 Th1 cells, CD4 Th2 cells are resistant to galectin-9 death due to alternative glycosylation. On Th2 cells, galectin-9 binds cell surface protein disulfide isomerase (PDI), increasing retention of PDI on the cell surface and altering the redox status at the plasma membrane. Cell surface PDI regulates integrin function on platelets and also enhances susceptibility of T cells to infection with HIV. We find that galectin-9 binding to PDI on Th2 cells results in increased cell migration through extracellular matrix via β3 integrins, identifying a unique mechanism to regulate T-cell migration. In addition, galectin-9 binding to PDI on T cells potentiates infection with HIV. We identify a mechanism for regulating cell surface redox status via a galectin-glycoprotein lattice, to regulate distinct T-cell functions.

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“…85 Notably, the orientation, rotational flexibility, and spacing of the CRDs present in bivalent or multimeric galectins may also determine differences in the recognition of specific glycan ligands on different cell types. 5,6,198,199 In an elegant study aimed at dissecting the structural features of galectin-1 and galectin-9 that contribute to their function, Bi and co-workers 198 designed a series of hybrid proteins that combined CRDs of these two lectins, connected with different peptide linkers. Using these constructs, the authors found that while the N-terminal CRD and linker peptide contributed to the potency of the lectins, the C-terminal CRD was the primary determinant of receptor recognition, death pathway signaling, and target cell susceptibility.…”

Section: ■ Galectins In Adaptive Immunitymentioning

confidence: 99%

“…These galectins were considerably more potent in binding to glycan ligands and cell surface glycoprotein receptors, as well as in triggering T-cell death, than native galectin-1 or a construct with a short rigid linker. 199 Thus, the increased potency of tandem repeat-type galectins compared with that of proto-type galectins is likely due to the ability of the linker domain to permit intermolecular CRD interactions, thus promoting higher-order multimerization and an increased level of lattice formation on the cell surface. Interestingly, from a pathophysiologic standpoint, in vivo formation of higherorder multivalent multimers by tandem repeat-type galectins may allow these lectins to exhibit significant biological effects at tissue concentrations much lower than those observed for proto-type galectins.…”

Section: ■ Galectins In Adaptive Immunitymentioning

confidence: 99%

When Galectins Recognize Glycans: From Biochemistry to Physiology and Back Again

et al. 2011

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In the past decade, increasing efforts have been devoted to the study of galectins, a family of evolutionarily conserved glycan-binding proteins with multifunctional properties. Galectins function, either intracellularly or extracellularly, as key biological mediators capable of monitoring changes occurring on the cell surface during fundamental biological processes such as cellular communication, inflammation, development, and differentiation. Their highly conserved structures, exquisite carbohydrate specificity, and ability to modulate a broad spectrum of biological processes have captivated a wide range of scientists from a wide spectrum of disciplines, including biochemistry, biophysics, cell biology, and physiology. However, in spite of enormous efforts to dissect the functions and properties of these glycan-binding proteins, limited information about how structural and biochemical aspects of these proteins can influence biological functions is available. In this review, we aim to integrate structural, biochemical, and functional aspects of this bewildering and ancient family of glycan-binding proteins and discuss their implications in physiologic and pathologic settings.

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Galectin multimerization and lattice formation are regulated by linker region structure

Abstract: The publishers would like to apologize for an error in the above paper, in which the joint First authorship was not accredited. It should have been acknowledged that Lesley A Earl and Shuguang Bi contributed equally to this work. We sincerely apologise for this error.

Cited by 6 publications

References 0 publications

Regulation of Transmembrane Signaling by Phase Separation

Regulation of Transmembrane Signaling by Phase Separation

Galectin-9 binding to cell surface protein disulfide isomerase regulates the redox environment to enhance T-cell migration and HIV entry

When Galectins Recognize Glycans: From Biochemistry to Physiology and Back Again

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