Modulating Cell‐Surface Receptor Signaling and Ion Channel Functions by In Situ Glycan Editing

Jiang, Hao; López-Aguilar, Aimé; Li, Meng; Gao, Zhongwei; Liu, Yani; Tian, Xiao; Yu, Guangli; Ovryn, Ben; Moremen, Kelley W.; Wu, Peng

doi:10.1002/ange.201706535

Cited by 6 publications

(7 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, due to the creation of the expression vector library encoding all known human glycosyltransferases by Moremen et al, any human glycosyltransferase of interest can now be produced as secreted catalytic domain GFP-fusion proteins in mammalian and insect cell hosts 47 . Studies by Boons, Steet and coworkers and by our own lab have demonstrated that several enzymes produced by this system are highly efficient for cell-surface chemoenzymatic glycan modification 2,9,48 . However, this approach is associated with relatively high cost.…”

Section: Discussionmentioning

confidence: 93%

“…Complementary to metabolic oligosaccharide engineering (MOE) 1 , chemoenzymatic glycan labeling and modification have emerged as valuable tools to modify glycan structures within a cellular environment 2–4 . Unlike MOE, which relies on a cell or an organisms’s own glycan biosynthetic mechinary to incorporate unnatural monosaccharides with linkage promiscuity, chemoenzymatic glycan modification utilizes a recombinant glycosyltransferase to transfer natural or unnatural monosaccharides with novel functions from activated nucleotide sugars to glycoconjugates on the cell surface with linkage specificity.…”

Section: Introductionmentioning

confidence: 99%

“…In their pioneering work, Sackstein, Xia et al, applied chemoenzymatic glycan modification based on human α1-3-fucosyltransferase (FT) to install α1-3-linked fucose (Fuc) onto the cell-surface, thereby creating E-selectin ligand, sLe X (NeuAcα2-3-Galβ1-4-(Fucα1-3)-Glc N Ac), so as to enhance the engraftment and trafficking of human multipotent mesenchymal stromal cells and cord blood cells 5,6 . In our previous work, we employed chemoenzymatic glycan modification to tune cell-surface receptor signaling and stem cell proliferation 2,7 . Combining this method with bioorthogonal click chemistry, several labs, including our own, have demonstrated that imaging and profiling of specific cellular glycans can be realized 8–10 .…”

Section: Introductionmentioning

confidence: 99%

“…Mammalian Golgi glycosyltransferases are type II transmembrane proteins 12 . For cell-surface glycan modification, truncated versions are often used, including human FT6 and FT7 and ST6Gal1, ST3Gal4, and ST3Gal1 2,5,9,13 . Bacterial glycosyltransferases, on the other hand, often lack the transmembrane domain and, therefore, are more easily expressed in Escherichia coli as soluble proteins.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Bacterial glycosyltransferase-mediated cell-surface chemoenzymatic glycan modification

Hong

Shi

et al. 2019

Nat Commun

Self Cite

View full text Add to dashboard Cite

Chemoenzymatic modification of cell-surface glycan structures has emerged as a complementary approach to metabolic oligosaccharide engineering. Here, we identify Pasteurella multocida α2-3-sialyltransferase M144D mutant, Photobacterium damsela α2-6-sialyltransferase, and Helicobacter mustelae α1-2-fucosyltransferase, as efficient tools for live-cell glycan modification. Combining these enzymes with Helicobacter pylori α1-3-fucosyltransferase, we develop a host-cell-based assay to probe glycan-mediated influenza A virus (IAV) infection including wild-type and mutant strains of H1N1 and H3N2 subtypes. At high NeuAcα2-6-Gal levels, the IAV-induced host-cell death is positively correlated with haemagglutinin (HA) binding affinity to NeuAcα2-6-Gal. Remarkably, an increment of host-cell-surface sialyl Lewis X (sLe X ) exacerbates the killing by several wild-type IAV strains and a previously engineered mutant HK68-MTA. Structural alignment of HAs from HK68 and HK68-MTA suggests formation of a putative hydrogen bond between Trp222 of HA-HK68-MTA and the C-4 hydroxyl group of the α1-3-linked fucose of sLe X , which may account for the enhanced host cell killing of that mutant.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Bacterial glycosyltransferase-mediated cell-surface chemoenzymatic glycan modification

Hong

Shi

et al. 2019

Nat Commun

Self Cite

View full text Add to dashboard Cite

show abstract

“…Note that the most important membrane transporters in cancer cells are the ATP-dependent Na + , K + , 2Cl − co-transporter NKCC1, the Na/K ATPase, cation channels, and the Na + /H + exchanger NHE1 [ 52 ]. Therefore, it seems reasonable to suggest that changes in the size and chemical composition of the membrane glycans at the melanoma cell surface are responsible for developmental and cell-specific variability in the biophysical and functional properties of many ion channels [ 53 ]. The present study evidenced that the structure of α 1-acid glycoprotein composing of ca.…”

Section: Resultsmentioning

confidence: 99%

Tracking of Glycans Structure and Metallomics Profiles in BRAF Mutated Melanoma Cells Treated with Vemurafenib

Nisiewicz

Kowalczyk

Sobiepanek

et al. 2021

IJMS

View full text Add to dashboard Cite

Nearly half of patients with advanced and metastatic melanomas harbor a BRAF mutation. Vemurafenib (VEM), a BRAF inhibitor, is used to treat such patients, however, responses to VEM are very short-lived due to intrinsic, adaptive and/or acquired resistance. In this context, we present the action of the B-Raf serine-threonine protein kinase inhibitor (vemurafenib) on the glycans structure and metallomics profiles in melanoma cells without (MeWo) and with (G-361) BRAF mutations. The studies were performed using α1-acid glycoprotein (AGP), a well-known acute-phase protein, and concanavalin A (Con A), which served as the model receptor. The detection of changes in the structure of glycans can be successfully carried out based on the frequency shifts and the charge transfer resistance after interaction of AGP with Con A in different VEM treatments using QCM-D and EIS measurements. These changes were also proved based on the cell ultrastructure examined by TEM and SEM. The LA-ICP-MS studies provided details on the metallomics profile in melanoma cells treated with and without VEM. The studies evidence that vemurafenib modifies the glycans structures and metallomics profile in melanoma cells harboring BRAF mutation that can be further implied in the resistance phenomenon. Therefore, our data opens a new avenue for further studies in the short-term addressing novel targets that hopefully can be used to improve the therapeutic regiment in advanced melanoma patients. The innovating potential of this study is fully credible and has a real impact on the global patient society suffering from advanced and metastatic melanomas.

show abstract

Systematic Interrogation of Cellular Signaling in Live Cells Using a Membrane‐Anchored DNA Multitasking Processor

Shan

et al. 2022

Angewandte Chemie

View full text Add to dashboard Cite

Systematic interrogation of correlative signaling components in their native environment is of great interest for dissecting sophisticated cellular signaling. However, it remains a challenge because of the lack of versatile and effective approaches. Herein, we propose a cell membrane‐anchored DNA multitasking processor acting as a “traffic light” for integrated analyses of cellular signal transduction. Enhanced and controllable inhibition of c‐Met signaling was achieved by membrane‐anchoring of DNA processors. Moreover, the multitasking capability of the DNA processor allowed the monitoring of correlative VEGF secretion induced by c‐Met activity regulation directly. By exploiting versatile aptameric nucleic acids, this modular designed DNA multitasking processor dissected how cell surface receptors coordinated with related components in live cells systematically. Therefore, it provides a powerful chemical tool for both fundamental cell biology research and precision medicine applications.

show abstract

Modulating Cell‐Surface Receptor Signaling and Ion Channel Functions by In Situ Glycan Editing

Abstract: Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Cited by 6 publications

References 39 publications

Bacterial glycosyltransferase-mediated cell-surface chemoenzymatic glycan modification

Bacterial glycosyltransferase-mediated cell-surface chemoenzymatic glycan modification

Tracking of Glycans Structure and Metallomics Profiles in BRAF Mutated Melanoma Cells Treated with Vemurafenib

Systematic Interrogation of Cellular Signaling in Live Cells Using a Membrane‐Anchored DNA Multitasking Processor

Contact Info

Product

Resources

About