Contribution of N-Linked Glycans to the Conformation and Function of Intercellular Adhesion Molecules (ICAMs)

Jiménez, David Álvarez; Roda-Navarro, Pedro; Springer, Timothy A.; Casasnovas, José M.

doi:10.1074/jbc.m412104200

Cited by 62 publications

(63 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cDNA for the complete extracellular region of human dectin-1 (amino acids [aa] 71 to 247, corresponding to stalk and carbohydrate recognition domains of the receptor) was cloned upstream of the human IgG1-Fc (Fc) genomic DNA in the mammalian expression vector pEF (30), bearing an amino-terminal Ig() chain signal peptide. The protein was transiently expressed in HEK293T cells transfected by the calcium phosphate method.…”

Section: Methodsmentioning

confidence: 99%

Candida albicans β-Glucan Exposure Is Controlled by the Fungal CEK1 -Mediated Mitogen-Activated Protein Kinase Pathway That Modulates Immune Responses Triggered through Dectin-1

et al. 2010

View full text Add to dashboard Cite

Innate immunity to Candida albicans depends upon the recognition of molecular patterns on the fungal cell wall. However, the masking of major components such as ␤-glucan seems to be a mechanism that fungi have evolved to avoid immune cell recognition through the dectin-1 receptor. Although the role of C. albicans mitogen-activated protein kinase (MAPK) pathways as virulence determinants has been established previously with animal models, the mechanism involved in this behavior is largely unknown. In this study we demonstrate that a disruption of the C. albicans extracellular signal-regulated kinase (ERK)-like 1 (CEK1)-mediated MAPK pathway causes enhanced cell wall ␤-glucan exposure, triggering immune responses more efficiently than the wild type, as measured by dectin-1-mediated specific binding and human dendritic cell (hDC)-and macrophage-mediated phagocytosis, killing, and activation of intracellular signaling pathways. At the molecular level, the disruption of CEK1 resulted in altered spleen tyrosine kinase (Syk), Raf-1, and ERK1/2 activations together with IB degradation on hDCs and increased dectin-1-dependent activator protein 1 (AP-1) activation on transfected cells. In addition, concurring with these altered pathways, we detected increased reactive oxygen species production and cytokine secretion. In conclusion, the CEK1-mediated MAPK pathway is involved in ␤-glucan exposure in a fungal pathogen, hence influencing dectin-1-dependent immune cell recognition, thus establishing this fungal intracellular signaling route as a promising novel therapeutic target.

show abstract

Section: Methodsmentioning

confidence: 99%

Candida albicans β-Glucan Exposure Is Controlled by the Fungal CEK1 -Mediated Mitogen-Activated Protein Kinase Pathway That Modulates Immune Responses Triggered through Dectin-1

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Bacterial lysis and purification of the inclusion bodies were carried out as described previously (26). Pellets were resuspended in 50 mM TRIS, 0.2 M NaCl, 5 mM EDTA, 5 mM DTT, pH 8.0 and lysozyme was added at a final concentration of 1 mg/ml.…”

Section: Ms/ms Ion Search and Peptidementioning

confidence: 99%

A Molecular Basis for the Presentation of Phosphorylated Peptides by HLA-B Antigens

Alpízar

Marino

Ramos-Fernández

et al. 2017

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

“…CAR has two N-glycosylation sites, one on each of its extracellular domains (N106 in D1 and N201 in D2). Glycosylation of ICAM-1 is not required for rhinovirus binding (19,24) or for poliovirus interaction with PVR (25). In contrast, the binding and infection efficiency of hepatitis A virus (HAV) depends on glycosylation of the HAV cellular receptor havcr-1, and deglycosylation results in decreased susceptibility of the cells to HAV infection (26).…”

mentioning

confidence: 99%

The Coxsackievirus and Adenovirus Receptor: Glycosylation and the Extracellular D2 Domain Are Not Required for Coxsackievirus B3 Infection

Pinkert

Röger

Kurreck

et al. 2016

J Virol

View full text Add to dashboard Cite

The coxsackievirus and adenovirus receptor (CAR) is a member of the immunoglobulin superfamily (IgSF) and functions as a receptor for coxsackie B viruses (CVBs). The extracellular portion of CAR comprises two glycosylated immunoglobulin-like domains, D1 and D2. CAR-D1 binds to the virus and is essential for virus infection; however, it is not known whether D2 is also important for infection, and the role of glycosylation has not been explored. To understand the function of these structural components in CAR-mediated CVB3 infection, we generated a panel of human (h) CAR deletion and substitution mutants and analyzed their functionality as CVB receptors, examining both virus binding and replication. Lack of glycosylation of the CAR-D1 or -D2 domains did not adversely affect CVB3 binding or infection, indicating that the glycosylation of CAR is not required for its receptor functions. Deletion of the D2 domain reduced CVB3 binding, with a proportionate reduction in the efficiency of virus infection. Replacement of D2 with the homologous D2 domain from chicken CAR, or with the heterologous type C2 immunoglobulin-like domain from IgSF11, another IgSF member, fully restored receptor function; however, replacement of CAR-D2 with domains from CD155 or CD80 restored function only in part. These data indicate that glycosylation of the extracellular domain of hCAR plays no role in CVB3 receptor function and that CAR-D2 is not specifically required. The D2 domain may function largely as a spacer permitting virus access to D1; however, the data may also suggest that D2 affects virus binding by influencing the conformation of D1. IMPORTANCE An important step in virus infection C oxsackie B viruses (CVBs) initiate infection of their host cells by interaction with the coxsackievirus and adenovirus receptor (CAR). An additional cell surface protein, decay-accelerating factor (DAF), promotes binding to the cell surface but is not sufficient for infection (1-3). CAR is a member of the immunoglobulin superfamily (IgSF) and is composed of two extracellular immunoglobulin-like domains, D1 (amino acid [aa] 20 to 139) and D2 (aa 142 to 229), as well as a typical hydrophobic transmembrane domain (TMD; aa 236 to 258) and an internal cytoplasmic domain (ICD; aa 259 to 365) (4). The extracellular immunoglobulin-like domains vary in their secondary structure by different ␤-strand folding. Whereas D1 shows a typical V-type fold structure, D2 has a C2-type immunoglobulin fold (5, 6). Several studies indicate a primary role for the D1 domain in CAR interactions with CVB3 (7) and adenovirus (8), as well as in CAR/CAR homophilic interactions (9-11). Although the isolated D1 domain, produced in Escherichia coli, binds adenovirus efficiently (8), the same D1 domain was found to bind poorly to CVB3 (7), suggesting a possible supporting role for the D2 domain during CAR/ CVB3 interaction.Numerous picornavirus receptors are members of the IgSF: intercellular adhesion molecule-1 (ICAM-1) is a receptor for coxsackievirus A21 (CAV21) and the ma...

show abstract

Contribution of N-Linked Glycans to the Conformation and Function of Intercellular Adhesion Molecules (ICAMs)

Cited by 62 publications

References 30 publications

Candida albicans β-Glucan Exposure Is Controlled by the Fungal CEK1 -Mediated Mitogen-Activated Protein Kinase Pathway That Modulates Immune Responses Triggered through Dectin-1

Candida albicans β-Glucan Exposure Is Controlled by the Fungal CEK1 -Mediated Mitogen-Activated Protein Kinase Pathway That Modulates Immune Responses Triggered through Dectin-1

A Molecular Basis for the Presentation of Phosphorylated Peptides by HLA-B Antigens

The Coxsackievirus and Adenovirus Receptor: Glycosylation and the Extracellular D2 Domain Are Not Required for Coxsackievirus B3 Infection

Contact Info

Product

Resources

About