Galectins at a glance

Johannes, Ludger; Jacob, Ralf; Leffler, Hakon

doi:10.1242/jcs.208884

Cited by 485 publications

(538 citation statements)

References 158 publications

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“…S10). Next we tested the galactophilic lectin galectin 3, which is known to bind primarily to β-galactoside residues and plays an important role in cell adhesion, macrophage activation, and apoptosis (32). As expected, we observed highly efficient partitioning of Alexa Fluor 488-labeled galectin-3 into the droplets (Fig.…”

Section: Resultssupporting

confidence: 67%

Lipid Sponge Droplets as Programmable Synthetic Organelles

Bhattacharya

Niederholtmeyer

Podolsky

et al. 2020

Preprint

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performed the biochemical, chemical, and imaging experiments. A.B., R.B., J.S., and S.K.S performed and analyzed the data for X-ray scattering experiments. A.B., H.N., and N.K.D wrote the manuscript. AbstractLiving cells segregate molecules and reactions in various subcellular compartments known as organelles. Spatial organization is likely essential for expanding the biochemical functions of synthetic reaction systems, including artificial cells. Many studies have attempted to mimic organelle functions using lamellar membrane-bound vesicles. However, vesicles typically suffer from highly limited transport across the membranes and an inability to mimic the dense membrane networks typically found in organelles such as the endoplasmic reticulum. Here we describe programmable synthetic organelles based on highly stable nonlamellar sponge phase droplets that spontaneously assemble from a single-chain galactolipid and nonionic detergents. Due to their nanoporous structure, lipid sponge droplets readily exchange materials with the surrounding environment. In addition, the sponge phase contains a dense network of lipid bilayers and nanometric aqueous channels, which allows different classes of molecules to partition based on their size, polarity, and specific binding motifs. The sequestration of biologically relevant macromolecules can be programmed by the addition of suitably functionalized amphiphiles to the droplets. We demonstrate that droplets can harbor functional soluble and transmembrane proteins, allowing for the co-localization and concentration of enzymes and substrates to enhance reaction rates. Droplets protect bound proteins from proteases, and these interactions can be engineered to be reversible and optically controlled. Our results show that lipid sponge droplets permit the facile integration of membrane-rich environments and selfassembling spatial organization with biochemical reaction systems. Significance statementOrganelles spatially and temporally orchestrate biochemical reactions in a cell to a degree of precision that is still unattainable in synthetic reaction systems. Additionally, organelles such as the endoplasmic reticulum (ER) contain highly interconnected and dense membrane networks that provide large reaction spaces for both transmembrane and soluble enzymes. We present lipid sponge droplets to emulate the functions of organelles such as the ER. We demonstrate that lipid sponge droplets can be programmed to internally concentrate specific proteins, host and accelerate biochemical transformations, and to rapidly and reversibly sequester and release proteins to control enzymatic reactions. The self-assembled and programmable nature of lipid sponge droplets will facilitate the integration of complex functions for bottom up synthetic biology.

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Section: Resultssupporting

confidence: 67%

Lipid Sponge Droplets as Programmable Synthetic Organelles

Bhattacharya

Niederholtmeyer

Podolsky

et al. 2020

Preprint

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“…Similarly, intracellular Galectin-3 has been proven to enhance phagocytosis in macrophages via its interaction with F-actin in the phagocytic cups (Sano et al, 2003;Serizawa et al, 2015). Intracellular ligands have been proposed to bind Galectins through protein-protein interactions independent of carbohydrate-mediated recognition although whether both proteins interact directly or through an intermediary molecule is not known (de Oliveira et al, 2015;Johannes et al, 2018;Shimura et al, 2004). Whether Galectin-9 function in our study is carbohydrate-independent remains to be elucidated but knockdown of Galectin-9 in the presence of other Galectins was sufficient to induce defects in actin polymerisation and cellular rigidity in DCs.…”

Section: Discussionmentioning

confidence: 99%

“…As such, Galectins can simultaneously interact with multiple glycoconjugates, thereby regulating the dynamics of glycosylated binding partners, limiting receptor internalisation and establishing membrane microdomains (Elola et al, 2015). Notably, Galectins are also abundantly expressed intracellularly although their cytosolic functions are not well characterised (Hsu et al, 2015a;Johannes et al, 2018;Liu et al, 2002;Liu and Rabinovich, 2005). Recently, Galectins have been discovered as novel regulators of several immune processes, such as T cell homeostasis, inflammation and immune disorders (de Oliveira et al, 2015;Rabinovich and Toscano, 2009;Sundblad et al, 2017;Thiemann and Baum, 2016).…”

Section: Introductionmentioning

confidence: 99%

Intracellular Galectin-9 controls dendritic cell function by maintaining plasma membrane rigidity

Cano

Tagit

Duffelen

et al. 2019

Preprint

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Extracellular Galectins constitute a novel mechanism of membrane protein organisation at the cell surface. Although Galectins are also highly expressed intracellularly, their cytosolic functions are poorly understood. Here, we investigated the role of Galectin-9 in dendritic cell (DC) surface organisation and function. By combining functional, super-resolution and atomic force microscopy experiments to analyse membrane stiffness, we identified intracellular Galectin-9 to be indispensable for plasma membrane integrity and structure in DCs. Galectin-9 knockdown studies revealed intracellular Galectin-9 to directly control cortical membrane structure via modulating Rac1 activity, providing the underlying mechanism of Galectin-9-dependent actin cytoskeleton organisation. Consequent to its role in maintaining plasma membrane structure, phagocytosis studies revealed that Galectin-9 was essential for C-type lectin receptor-mediated pathogen uptake by human DCs. This was confirmed by the impaired phagocytic capacity of Galectin-9-null murine DCs. Together, this study demonstrates a novel role for intracellular Galectin-9 in modulating DC function, which may be evolutionary conserved.

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“…Galectin-1, the first galectin to be characterized, is known to play an important role in cellular homeostasis, neoplastic progression and metastasis in a variety of tissues and organs (47).…”

Section: Discussionmentioning

confidence: 99%

Galectin-1 promotes the invasion of bladder cancer urothelia through their matrix milieu

Balakrishnan

Pally

Gondkar

et al. 2018

Preprint

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The progression of carcinoma of the urinary bladder involves migration of cancer epithelia through their surrounding tissue matrix microenvironment. This was experimentally confirmed when a gender-and grade-diverse set of bladder cancer cell lines were cultured in pathomimetic three-dimensional laminin-rich environments. The high-grade cells, particularly female, formed multicellular invasive morphologies in 3D. In comparison, low-and intermediategrade counterparts showed growth-restricted phenotypes. A proteomic approach combining mass spectrometry and bioinformatics analysis identified the estrogen-driven lactose-binding lectin Galectin-1 (GAL-1) as a putative candidate that could drive this invasion. Expression ofLGALS1, the gene encoding GAL-1 showed an association with tumor grade progression in bladder cell lines. Immunohisto-and cyto-chemical experiments suggested greater extracellular levels of GAL-1 in 3D cultures of high-grade bladder cells and cancer tissues. High levels of GAL-1 associated with increased proliferation-and adhesion-of bladder cancer cells when grown on laminin-rich matrices. Pharmacological inhibition and Gal-1 knockdown in high-grade female cells decreased their adhesion to, and viability on, laminin-rich substrata. Higher GAL-1 also correlated with reduced E-cadherin and increased N-cadherin levels in consonance with a mesenchymal-like phenotype that we observed in 3D culture. The inhibition of GAL-1 reversed the stellate invasive phenotype to a more growth-restricted one in high-grade cells embedded within both basement-membrane-like and stromal collagenous matrix scaffolds. Finally, inhibition of GAL-1 specifically altered cell surface sialic acids, suggesting the mechanism by which the levels of GAL-1 may underlie the aggression and poor prognosis of invasive bladder cancer, especially in women.

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Galectins at a glance

Cited by 485 publications

References 158 publications

Lipid Sponge Droplets as Programmable Synthetic Organelles

Lipid Sponge Droplets as Programmable Synthetic Organelles

Intracellular Galectin-9 controls dendritic cell function by maintaining plasma membrane rigidity

Galectin-1 promotes the invasion of bladder cancer urothelia through their matrix milieu

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