Polysialylated Neuropilin-2 Is Expressed on the Surface of Human Dendritic Cells and Modulates Dendritic Cell-T Lymphocyte Interactions

Curreli, Sabrina; Arany, Zita; Gerardy‐Schahn, Rita; Mann, Dean L.; Stamatos, Nicholas M.

doi:10.1074/jbc.m702965200

Cited by 163 publications

(185 citation statements)

References 49 publications

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“…It was first observed on salmonid egg polysialoglycoprotein, PSGP (49), and later found on neuropilin-2, CD36, unidentified proteins in the RBL-1 rat basophilic leukemia cell line, and several NCAM mutants, such as those lacking the FN1 ␣-helix or QVQ sequences, and the truncated NCAM protein NCAM7 (29,30,38,40,50). In addition, we frequently observe a small amount of O-glycan polysialylation in full-length NCAM (see Fig.…”

Section: Discussionmentioning

confidence: 94%

“…These are the ␣ subunit of the voltage-dependent sodium channel (28), the scavenger receptor CD36 found in milk (29), neuropilin-2 expressed on dendritic cells (30), and the polySTs themselves (autopolysialylation) (31,32). Recently, polysialic acid was reported to be present on another member of the immunoglobulin superfamily of proteins, the synaptic cell adhesion molecule SynCAM 1 (33).…”

Section: The Neural Cell Adhesion Molecule (Ncam)mentioning

confidence: 99%

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Sequences from the First Fibronectin Type III Repeat of the Neural Cell Adhesion Molecule Allow O-Glycan Polysialylation of an Adhesion Molecule Chimera

Foley

Swartzentruber

Thompson

et al. 2010

Journal of Biological Chemistry

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Polysialic acid is a developmentally regulated, anti-adhesive polymer that is added to N-glycans on the fifth immunoglobulin domain (Ig5) of the neural cell adhesion molecule (NCAM). We found that the first fibronectin type III repeat (FN1) of NCAM is required for the polysialylation of N-glycans on the adjacent Ig5 domain, and we proposed that the polysialyltransferases recognize specific sequences in FN1 to position themselves for Ig5 N-glycan polysialylation. Other studies identified a novel FN1 acidic surface patch and ␣-helix that play roles in NCAM polysialylation. Here, we characterize the contribution of two additional FN1 sequences, Pro The neural cell adhesion molecule (NCAM)2 is a member of the immunoglobulin superfamily. It is expressed on the cell surface where it engages in homophilic and heterophilic interactions, resulting in cell adhesion and modulation of signal transduction cascades (reviewed in Refs. 1, 2). In the developing embryo and neonate, NCAM is modified by the addition of long chains of ␣2,8-polysialic acid (3, 4). The presence of this highly hydrated and negatively charged carbohydrate polymer disrupts overall cell adhesion and allows cell migration (5-7). Polysialylation is catalyzed by the polysialyltransferases (polySTs), . NCAM polysialylation is critical during embryogenesis and early postnatal development. Mice that are null for both polySTs are born at Mendelian ratios but have severe neuronal defects, fail to thrive, and the majority die within 4 weeks of birth (12). Simultaneous deletion of NCAM and the polySTs rescues the lethal phenotype, indicating that polysialic acid is required to down-regulate the adhesive properties of NCAM during development (12). In addition, using varying allelic combinations of ST8SiaIV, ST8SiaII, and NCAM, Hildebrandt et al. (13) demonstrated that an aberrant increase in the level of unpolysialylated NCAM caused defects in brain connectivity in postnatal day 1 mice.NCAM is mainly unpolysialylated in the adult brain (3, 4). However, polysialylated NCAM does persist in specific regions of the central nervous system, including the olfactory bulb and hippocampus, where it functions in cell migration, synaptic plasticity, and repair (14 -17). Highly polysialylated NCAM is also re-expressed in several cancers, including neuroblastoma, glioma, small cell and non-small cell lung tumors, and Wilms' tumor, where it has been suggested to promote cancer invasiveness (18 -23). Recently, polysialylated NCAM has been shown to enhance metastasis of a murine model of lung cancer (24) and has been implicated in colorectal carcinoma progression (25). In addition, polysialic acid has been demonstrated to be involved in hematopoietic development (26,27). For example, ST8SiaIV Ϫ/Ϫ mice have reduced thymocyte numbers due to fewer progenitor cells mobilizing to the thymus (27).Although NCAM is by far the most abundant and well documented polysialylated protein, it is striking that only six other polysialylated glycoproteins have been identified. These are the ␣ subu...

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Section: Discussionmentioning

confidence: 94%

Section: The Neural Cell Adhesion Molecule (Ncam)mentioning

confidence: 99%

Sequences from the First Fibronectin Type III Repeat of the Neural Cell Adhesion Molecule Allow O-Glycan Polysialylation of an Adhesion Molecule Chimera

Foley

Swartzentruber

Thompson

et al. 2010

Journal of Biological Chemistry

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“…Flow cytometric analyses of total wildtype (WT) bone marrow comparing polySia and c-Kit expression (A). We studied four populations: PSA neg /Kit high (1), PSA low /Kit high (2), PSA high / Kit high (3), and PSA low /Kit low (4). These subsets were present in ST8Sia II Ϫ/Ϫ mice, but absent from ST8Sia IV Ϫ/Ϫ animals.…”

Section: Tumor Challengementioning

confidence: 99%

Polysialic Acid, a Glycan with Highly Restricted Expression, Is Found on Human and Murine Leukocytes and Modulates Immune Responses

Drake¹,

Nathan²,

Stock³

et al. 2008

The Journal of Immunology

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Polysialic acid (polySia) is a large glycan with restricted expression, typically found attached to the protein scaffold neural cell adhesion molecule (NCAM). PolySia is best known for its proposed role in modulating neuronal development. Its presence and potential functions outside the nervous systems are essentially unexplored. Herein we show the expression of polySia on hematopoietic progenitor cells, and demonstrate a role for this glycan in immune response using both acute inflammatory and tumor models. Specifically, we found that human NK cells modulate expression of NCAM and the degree of polymerization of its polySia glycans according to activation state. This contrasts with the mouse, where polySia and NCAM expression are restricted to multipotent hematopoietic progenitors and cells developing along a myeloid lineage. Sialyltransferase 8Sia IV−/− mice, which lacked polySia expression in the immune compartment, demonstrated an increased contact hypersensitivity response and decreased control of tumor growth as compared with wild-type animals. This is the first demonstration of polySia expression and regulation on myeloid cells, and the results in animal models suggest a role for polySia in immune regulation.

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“…For example, PSA-NCAM is expressed in regenerating areas of the adult brain such as the olfactory bulb and hippocampus (2,3) and also in leukocytes (4), but most other tissues are thought to contain little PSA. In addition to NCAM, synaptic cell adhesion molecule 1 (5), the ␣ subunit of the voltage-sensitive sodium channel (6), the integrin ␣5 subunit (7), the scavenger receptor CD36 (8), neuropilin-2 (9), and the polysialyltransferases that produce PSA, ST8SiaII, and ST8SiaIV, also known as STX and PST, respectively (10), are also modified with PSA. Apart from modulating NCAM adhesive interactions (3), the specific functional role(s) of polysialylation, the relative distribution of polysialylated versus unmodified protein, and the reasons for differences in polysialylation of proteins (other than NCAM) are unknown.…”

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confidence: 99%

The Expression Profile of De-N-acetyl Polysialic Acid (NeuPSA) in Normal and Diseased Human Tissue

Nakano¹,

Steirer²,

Moe³

2011

Journal of Biological Chemistry

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Polysialylated Neuropilin-2 Is Expressed on the Surface of Human Dendritic Cells and Modulates Dendritic Cell-T Lymphocyte Interactions

Cited by 163 publications

References 49 publications

Sequences from the First Fibronectin Type III Repeat of the Neural Cell Adhesion Molecule Allow O-Glycan Polysialylation of an Adhesion Molecule Chimera

Sequences from the First Fibronectin Type III Repeat of the Neural Cell Adhesion Molecule Allow O-Glycan Polysialylation of an Adhesion Molecule Chimera

Polysialic Acid, a Glycan with Highly Restricted Expression, Is Found on Human and Murine Leukocytes and Modulates Immune Responses

The Expression Profile of De-N-acetyl Polysialic Acid (NeuPSA) in Normal and Diseased Human Tissue

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