Structural Basis for Galectin-1-dependent Pre-B Cell Receptor (Pre-BCR) Activation

Elantak, Latifa; Espéli, Marion; Boned, Annie; Bornet, Olivier; Bonzi, Jeremy; Gauthier, Laurent; Feracci, Mikaël; Roché, Philippe; Guerlesquin, Françoise; Schiff, Claudine

doi:10.1074/jbc.m112.395152

Cited by 50 publications

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“…To establish the biological relevance of the differences observed on glycan array screenings, we performed glycomic analysis of Nalm6 pre-BII and OP9 stromal cell lines using lectin microarray experiments. These cell lines have been chosen since they have been used in many functional assays [18][19][20]26 to study the role of GAL1 and GAL1/pre-BCR interaction for pre-BCR relocalization and signalling. We have shown previously that, similarly to normal pre-BII cells, the Nalm6 pre-B cell line expresses preBCRs and integrins required for the formation of the pre-B cell synapse and the induction of an efficient pre-BCR signal [18][19][20]26 .…”

Section: Gal1 Carbohydrate-binding Specificity When Bound To K5-urmentioning

confidence: 99%

“…These cell lines have been chosen since they have been used in many functional assays [18][19][20]26 to study the role of GAL1 and GAL1/pre-BCR interaction for pre-BCR relocalization and signalling. We have shown previously that, similarly to normal pre-BII cells, the Nalm6 pre-B cell line expresses preBCRs and integrins required for the formation of the pre-B cell synapse and the induction of an efficient pre-BCR signal [18][19][20]26 . In addition, OP9 stromal cells were shown to strongly support normal pre-BII cell differentiation, due to the expression of GAL1 and integrin ligands required for the formation of the pre-B cell synapse 20 .…”

Section: Gal1 Carbohydrate-binding Specificity When Bound To K5-urmentioning

confidence: 99%

“…We hypothesized that this close proximity of the two interacting surfaces might then influence the carbohydrate-binding event when the l5-UR peptide is bound to GAL1. Interestingly, on l5-UR binding, the lactose-binding activity of GAL1 undergoes a fourfold decrease, while no binding affinity changes have been observed for GAL1/ l5-UR interaction in the presence versus in the absence of lactose 26 . These modulations suggest that the pre-BCR could modulate GAL1 affinity for specific glycoproteins 26 by a mechanism that would be a strategic step at the synapse level to modify the crosslinked lattices.…”

mentioning

confidence: 99%

“…Interestingly, on l5-UR binding, the lactose-binding activity of GAL1 undergoes a fourfold decrease, while no binding affinity changes have been observed for GAL1/ l5-UR interaction in the presence versus in the absence of lactose 26 . These modulations suggest that the pre-BCR could modulate GAL1 affinity for specific glycoproteins 26 by a mechanism that would be a strategic step at the synapse level to modify the crosslinked lattices. Our hypothesis is supported by a recent study on a non-natural peptide, Anginex, suggesting that this peptide is able to enhance GAL1 carbohydrate-binding affinity for glycoproteins 27 .…”

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confidence: 99%

“…The N terminus of l5 and the C terminus of VpreB contain unique regions (l5-UR and VpreB-UR, respectively) crucial for pre-BCR cell surface expression 24,25 and pre-BCR activation 18,24 . We recently found that GAL1 interacts with a l5-UR motif, l5-UR , of the pre-BCR that adopts a stable helical conformation that docks onto a GAL1 hydrophobic surface adjacent to the CBS 26 . We hypothesized that this close proximity of the two interacting surfaces might then influence the carbohydrate-binding event when the l5-UR peptide is bound to GAL1.…”

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confidence: 99%

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Pre-B cell receptor binding to galectin-1 modifies galectin-1/carbohydrate affinity to modulate specific galectin-1/glycan lattice interactions

et al. 2015

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Galectins are glycan-binding proteins involved in various biological processes including cell/cell interactions. During B-cell development, bone marrow stromal cells secreting galectin-1 (GAL1) constitute a specific niche for pre-BII cells. Besides binding glycans, GAL1 is also a pre-B cell receptor (pre-BCR) ligand that induces receptor clustering, the first checkpoint of B-cell differentiation. The GAL1/pre-BCR interaction is the first example of a GAL1/unglycosylated protein interaction in the extracellular compartment. Here we show that GAL1/pre-BCR interaction modifies GAL1/glycan affinity and particularly inhibits binding to LacNAc containing epitopes. GAL1/pre-BCR interaction induces local conformational changes in the GAL1 carbohydrate-binding site generating a reduction in GAL1/glycan affinity. This fine tuning of GAL1/glycan interactions may be a strategic mechanism for allowing pre-BCR clustering and pre-BII cells departure from their niche. Altogether, our data suggest a novel mechanism for a cell to modify the equilibrium of the GAL1/glycan lattice involving GAL1/unglycosylated protein interactions.

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Section: Gal1 Carbohydrate-binding Specificity When Bound To K5-urmentioning

confidence: 99%

Section: Gal1 Carbohydrate-binding Specificity When Bound To K5-urmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Pre-B cell receptor binding to galectin-1 modifies galectin-1/carbohydrate affinity to modulate specific galectin-1/glycan lattice interactions

et al. 2015

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B Lymphocytes: Receptors

DeFranco

2015

Encyclopedia of Life Sciences

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B lymphocytes can synthesise Ig heavy chains that are either secreted or membrane‐bound, the latter having a transmembrane domain and a short cytoplasmic domain. Membrane‐bound Ig heavy chains and Ig light chains assemble in the ER with each other and with a heterodimer of Igα and Igβ, which mediate signalling and internalisation functions. The complex of these four polypeptides is called the B cell antigen receptor (BCR). BCR signalling occurs via three types of tyrosine kinases. Src‐family kinases phosphorylate the two tyrosine‐containing motif in the cytoplasmic domains of Igα and Igβ (the ITAMs), which recruits a second type of tyrosine kinase Syk. Syk is responsible for most downstream signalling, although calcium and diacylglycerol also require a third tyrosine kinase Btk. BCR signalling pathways are central to virtually all aspects of B cell biology, as they are required for B cell development, tolerance induction, survival and activation. Key Concepts Naïve B cells express their immunoglobulin as a cell surface receptor for antigen, called the BCR (B cell receptor for antigen). In developing precursors of B cells, the successful generation of an immunoglobulin heavy chain is sensed by the incorporation of that heavy chain into pre‐BCR molecules, which exhibit constitutive signalling. Signalling by the BCR controls development, survival and activation of B cells in a manner that is dependent on the developmental stage or activation state of the B cell. This signalling is important both for tolerisation of self‐reactive B cells and for activation of B cells recognising foreign antigen. Co‐receptors that recognise complement components, sialic acid residues, or IgG bound to antigens strongly enhance or inhibit signalling by the BCR to aid in self‐non‐self‐discrimination. The BCR is also an endocytic receptor that delivers antigen to internal compartments where protein antigens are processed into peptides and loaded onto MHC class II molecules to facilitate interactions with T cells, which are essential for production of high‐affinity antibodies. Defects in generation of BCRs or signalling components of the BCR result in B cell immunodeficiencies, the most common of which is due to loss‐of‐function mutations of the intracellular protein tyrosine kinase Btk, referred to as X‐linked agammaglobulinemia. B cell malignancies often have activated BCR signalling as a driver of their proliferation and/or survival, and selective Btk inhibitors are now approved therapeutics for some types of B cell malignancies.

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Detection of malignancy‐associated phosphoproteome changes in human colorectal cancer induced by cell surface binding of growth‐inhibitory galectin‐4

et al. 2018

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Emerging evidence on efficient tumor growth regulation by endogenous lectins directs interest to determine on a proof‐of‐principle level the range of information on alterations provided by full‐scale analysis using phosphoproteomics. In our pilot study, we tested galectin‐4 (gal‐4) that is a growth inhibitor for colon cancer cells (CRC), here working with the LS 180 line. In order to cover monitoring of short‐ and long‐term effects stable isotope labeling by amino acids in cell culture‐based quantitative phosphoproteomic analyses were conducted on LS 180 cell preparations collected 1 and 72 h after adding gal‐4 to the culture medium. After short‐term treatment, 981 phosphosites, all of them S/T based, were detected by phosphoproteomics. Changes higher than 1.5‐fold were seen for eight sites in seven proteins. Most affected were the BET1 homolog (BET1), whose level of phosphorylation at S50 was about threefold reduced, and centromere protein F (CENPF), extent of phosphorylation at S3119 doubling in gal‐4‐treated cells. Phosphoproteome analysis after 72 h of treatment revealed marked changes at 33 S/T‐based phosphosites from 29 proteins. Prominent increase of phosphorylation was observed for cofilin‐1 at position S3. Extent of phosphorylation of the glutamine transporter SLC1A5 at position S503 was decreased by a factor of 3. Altered phosphorylation of BET1, CENPF, and cofilin‐1 as well as a significant effect of gal‐4 treatment on glutamine uptake by cells were substantiated by independent methods in the Vaco 432, Colo 205, CX 1, and HCT 116 cell lines. With the example of gal‐4 which functions as a tumor suppressor in CRC cells, we were able to prove that cell surface binding of the lectin not only markedly influences the cell proteome, but also has a bearing on malignancy‐associated intracellular protein phosphorylation. These results underscore the potential of this approach to give further work on elucidating the details of signaling underlying galectin‐triggered growth inhibition a clear direction. © 2018 IUBMB Life, 71(3):364–375, 2019

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Structural Basis for Galectin-1-dependent Pre-B Cell Receptor (Pre-BCR) Activation

Cited by 50 publications

References 36 publications

Pre-B cell receptor binding to galectin-1 modifies galectin-1/carbohydrate affinity to modulate specific galectin-1/glycan lattice interactions

Pre-B cell receptor binding to galectin-1 modifies galectin-1/carbohydrate affinity to modulate specific galectin-1/glycan lattice interactions

B Lymphocytes: Receptors

Detection of malignancy‐associated phosphoproteome changes in human colorectal cancer induced by cell surface binding of growth‐inhibitory galectin‐4

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