Neuronal Signaling by Thy-1 in Nanodomains With Specific Ganglioside Composition: Shall We Open the Door to a New Complexity?

Ilić, Katarina; Auer, Benedikt; Mlinac-Jerkovic, Kristina; Herrera-Molina, Rodrigo

doi:10.3389/fcell.2019.00027

Cited by 12 publications

(14 citation statements)

References 108 publications

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“…LRs were isolated using discontinuous sucrose density centrifugation, by an optimized procedure modified in our Laboratory (Ilic et al., 2019; Puljko et al., 2021). Frozen cortical brain tissue samples were thawed on ice and 70 ± 5 mg of tissue was homogenized in 3 ml of detergent‐free homogenization buffer (50 mM Tris (pH = 8), 150 mM NaCl, 1 mM MgCl 2 , 1 mM CaCl 2 , and protease inhibitors 1 mM phenylmethylsulfonyl fluoride (PMSF), 5 mM NaF, 1 mM Na 3 VO 4 , and 1% protease inhibitor cocktail) containing 0.32 M sucrose with 30 strokes in a Potter‐Elvehjem glass homogenizer with a Teflon pestle.…”

Section: Methodsmentioning

confidence: 99%

Who's in, who's out? Re‐evaluation of lipid raft residents

Mlinac-Jerkovic

Ilić

Zjalić

et al. 2021

Journal of Neurochemistry

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Lipid rafts, membrane microdomains enriched with (glyco)sphingolipids, cholesterol, and select proteins, act as cellular signalosomes. Various methods have been used to separate lipid rafts from bulk (non‐raft) membranes, but most often, non‐ionic detergent Triton X‐100 has been used in their isolation. However, Triton X‐100 is a reported disruptor of lipid rafts. Histological evidence confirmed raft disruption by Triton X‐100, but remarkably revealed raft stability to treatment with a related polyethylene oxide detergent, Brij O20. We report isolation of detergent‐resistant membranes from mouse brain using Brij O20 and its use to determine the distribution of major mammalian brain gangliosides, GM1, GD1a, GD1b and GT1b. A different distribution of gangliosides—classically used as a raft marker—was discovered using Brij O20 versus Triton X‐100. Immunohistochemistry and imaging mass spectrometry confirm the results. Use of Brij O20 results in a distinctive membrane distribution of gangliosides that is not all lipid raft associated, but depends on the ganglioside structure. This is the first report of a significant proportion of gangliosides outside raft domains. We also determined the distribution of proteins functionally related to neuroplasticity and known to be affected by ganglioside environment, glutamate receptor subunit 2, amyloid precursor protein and neuroplastin and report the lipid raft populations of these proteins in mouse brain tissue. This work will enable more accurate lipid raft analysis with respect to glycosphingolipid and membrane protein composition and lead to improved resolution of lipid–protein interactions within biological membranes.

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Section: Methodsmentioning

confidence: 99%

Who's in, who's out? Re‐evaluation of lipid raft residents

Mlinac-Jerkovic

Ilić

Zjalić

et al. 2021

Journal of Neurochemistry

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“…This dynamic process requires equally dynamic changes of the interactions taking place between Thy-1/CD90 and its binding partners. Thus, the lipid-protein composition of the microdomains where Thy-1/CD90 resides, and which are known to undergo constant, rapid, and dynamic organization [reviewed in Ilic et al (2019)] are ideal platforms to allow the fluid and active arrangements of their components.…”

Section: Thy-1/cd90 Cell Adhesion Molecule a Receptor Or A Ligand?mentioning

confidence: 99%

“…Recent reports have indicated that the interaction of Thy-1/CD90 with integrin mediates association of many different cell types [reviewed in Kong et al (2013), Furlong et al (2018), Hagood (2019), Hu and Barker (2019), Ilic et al (2019), Morris (2018), and Picke et al (2018b)]. For example, Thy-1/CD90 plays an important role as a β 3 integrin ligand in fibroblasts and cancer cells.…”

Section: Thy-1/cd90 In Cell-to-cell Interactionsmentioning

confidence: 99%

“…Thy-1/CD90 locates in rafts that associate with actin and possess saturated lipids, whereas PrPC is in microdomains with more unsaturated and longer chain lipids (Brügger et al, 2004), which do not contact the actin cytoskeleton (Chen et al, 2008; Morris et al, 2011). Additionally, lipid and protein composition of these raft structures is dynamic and arranged in nanodomains that rapidly reorganize and change their components to control signal transduction events [reviewed in Ilic et al (2019)].…”

Section: Extracellular Thy-1/cd90-linked Plasma Membrane-associated Pmentioning

confidence: 99%

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Thy-1/CD90 a Bidirectional and Lateral Signaling Scaffold

Leyton

Díaz

Martı́nez

et al. 2019

Front. Cell Dev. Biol.

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Thy-1/CD90 is a glycoprotein attached to the outer face of the plasma membrane with various functions, which depend on the context of specific physiological or pathological conditions. Many of these reported functions for Thy-1/CD90 arose from studies by our group, which identified the first ligand/receptor for Thy-1/CD90 as an integrin. This finding initiated studies directed toward unveiling the molecular mechanisms that operate downstream of Thy-1/CD90 activation, and its possible interaction with proteins in the membrane plane to regulate their function. The association of Thy-1/CD90 with a number of cell surface molecules allows the formation of extra/intracellular multiprotein complexes composed of various ligands and receptors, extracellular matrix proteins, intracellular signaling proteins, and the cytoskeleton. The complexes sense changes that occur inside and outside the cells, with Thy-1/CD90 at the core of this extracellular molecular platform. Molecular platforms are scaffold-containing microdomains where key proteins associate to prominently influence cellular processes and behavior. Each component, by itself, is less effective, but when together with various scaffold proteins to form a platform, the components become more specific and efficient to convey the messages. This review article discusses the experimental evidence that supports the role of Thy-1/CD90 as a membrane-associated platform (ThyMAP).

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“…Ganglioside head groups, protruding toward the extracellular space, significantly contribute to the cell glycocalyx and are major determinants of the features of the cell surface. In particular, they modulate complex interactions with other molecules sitting on the same cellular membrane ( cis interactions) or soluble molecules present in the extracellular environment or with molecules associated with the surface of other cells ( trans interactions) (reviewed in [2,23]). It is thus conceivable that the effects of A2B5 gangliosides are exerted by modulating the activity of receptors and their following signaling cascades [24].…”

Section: Discussionmentioning

confidence: 99%

Glycolipids Recognized by A2B5 Antibody Promote Proliferation, Migration, and Clonogenicity in Glioblastoma Cells

Baeza-Kallee

Bergès

Soubéran

et al. 2019

Cancers

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A2B5+ cells isolated from human glioblastomas exhibit cancer stem cell properties. The A2B5 epitope belongs to the sialoganglioside family and is synthetized by the ST8 alpha-N-acetyl-neuraminidase α-2,8-sialyltransferase 3 (ST8SIA3) enzyme. Glycolipids represent attractive targets for solid tumors; therefore, the aim of this study was to decipher A2B5 function in glioblastomas. To this end, we developed cell lines expressing various levels of A2B5 either by genetically manipulating ST8SIA3 or by using neuraminidase. The overexpression of ST8SIA3 in low-A2B5-expressing cells resulted in a dramatic increase of A2B5 immunoreactivity. ST8SIA3 overexpression increased cell proliferation, migration, and clonogenicity in vitro and tumor growth when cells were intracranially grafted. Conversely, lentiviral ST8SIA3 inactivation in low-A2B5-expressing cells resulted in reduced proliferation, migration, and clonogenicity in vitro and extended mouse survival. Furthermore, in the shST8SIA3 cells, we found an active apoptotic phenotype. In high-A2B5-expressing cancer stem cells, lentiviral delivery of shST8SIA3 stopped cell growth. Neuraminidase treatment, which modifies the A2B5 epitope, impaired cell survival, proliferation, self-renewal, and migration. Our findings prove the crucial role of the A2B5 epitope in the promotion of proliferation, migration, clonogenicity, and tumorigenesis, pointing at A2B5 as an attractive therapeutic target for glioblastomas.

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Neuronal Signaling by Thy-1 in Nanodomains With Specific Ganglioside Composition: Shall We Open the Door to a New Complexity?

Cited by 12 publications

References 108 publications

Who's in, who's out? Re‐evaluation of lipid raft residents

Who's in, who's out? Re‐evaluation of lipid raft residents

Thy-1/CD90 a Bidirectional and Lateral Signaling Scaffold

Glycolipids Recognized by A2B5 Antibody Promote Proliferation, Migration, and Clonogenicity in Glioblastoma Cells

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