Phosphorylation of Neuroglycan C, a Brain-specific Transmembrane Chondroitin Sulfate Proteoglycan, and Its Localization in the Lipid Rafts

Yamauchi, Shoji; Tokita, Yoshihito; Aono, Sachiko; Matsui, Fumiko; Shuo, Takuya; Ito, Hidenori; Kato, Kanefusa; Kasahara, Kohji; Oohira, Atsuhiko

doi:10.1074/jbc.m200909200

Cited by 18 publications

(15 citation statements)

References 60 publications

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“…Interestingly, both syndecans and chemokine receptors enhance HIV-1 transcytosis through PGECs. Previous studies showed that syndecans are associated with lipid rafts (22,33,54,56,65) and form complexes with CXCR4 and CCR5 on the cell surface (54). This suggests the possibility that syndecans and chemokine receptors are in close proximity on the surface of PGECs and that they cooperate for successful cell-free virus transcytosis.…”

Section: Discussionmentioning

confidence: 92%

Cell-Free Human Immunodeficiency Virus Type 1 Transcytosis through Primary Genital Epithelial Cells

Bobardt

Chatterji

Selvarajah

et al. 2007

J Virol

145

194

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Although the transport of human immunodeficiency virus type 1 (HIV-1) through the epithelium is critical for HIV-1 colonization, the mechanisms controlling this process remain obscure. In the present study, we investigated the transcellular migration of HIV-1 as a cell-free virus through primary genital epithelial cells (PGECs). The absence of CD4 on PGECs implicates an unusual entry pathway for HIV-1. We found that syndecans are abundantly expressed on PGECs and promote the initial attachment and subsequent entry of HIV-1 through PGECs. Although CXCR4 and CCR5 do not contribute to HIV-1 attachment, they enhance viral entry and transcytosis through PGECs. Importantly, HIV-1 exploits both syndecans and chemokine receptors to ensure successful cell-free transport through the genital epithelium. HIV-1-syndecan interactions rely on specific residues in the V3 of gp120 and specific sulfations within syndecans. We found no obvious correlation between coreceptor usage and the capacity of the virus to transcytose. Since viruses isolated after sexual transmission are mainly R5 viruses, this suggests that the properties conferring virus replication after transmission are distinct from those conferring cell-free virus transcytosis through the genital epithelium. Although we found that cell-free HIV-1 crosses PGECs as infectious particles, the efficiency of transcytosis is extremely poor (less than 0.02% of the initial inoculum). This demonstrates that the genital epithelium serves as a major barrier against HIV-1. Although one cannot exclude the possibility that limited passage of cell-free HIV-1 transcytosis through an intact genital epithelium occurs in vivo, it is likely that the establishment of infection via cell-free HIV-1 transmigration is a rare event.

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Section: Discussionmentioning

confidence: 92%

Cell-Free Human Immunodeficiency Virus Type 1 Transcytosis through Primary Genital Epithelial Cells

Bobardt

Chatterji

Selvarajah

et al. 2007

J Virol

145

194

View full text Add to dashboard Cite

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“…They postulated that proteoglycans facilitate HIV-1 entry into BMECs, either by rescuing HIV-1 from abortive endocytosis or by directing HIV-1 particles into safe transcytosis routes (8). Given that we and others showed that gp120 serves as the main ligand for HSPGs (15,54,72,96), it is difficult to imagine that HSPGs and CSPGs abundantly expressed on BMECs would not, at least in part, contribute to the initial attachment of HIV-1 to BMECs. Nevertheless, these apparent discrepancies may arise from the cell origin or cell culture conditions.…”

Section: Discussionmentioning

confidence: 99%

Contribution of Proteoglycans to Human Immunodeficiency Virus Type 1 Brain Invasion

Bobardt

Salmon

Wang

et al. 2004

J Virol

105

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As a neurotropic virus, human immunodeficiency virus type 1 (HIV-1) invades the brain and causes severe neuronal, astrocyte, and myelin damage in AIDS patients. To gain access to the brain, HIV-1 must migrate through brain microvascular endothelial cells (BMECs), which compose the blood-brain barrier (BBB). Given that BMECs lack the entry receptor CD4, HIV-1 must use receptors distinct from CD4 to enter these cells. We previously reported that cell surface proteoglycans serve as major HIV-1 receptors on primary human endothelial cells. In this study, we examined whether proteoglycans also impact cell-free HIV-1 invasion of the brain. Using an artificial BBB transmigration assay, we found that both heparan and chondroitin sulfate proteoglycans (HSPGs and CSPGs, respectively) are abundantly expressed on primary BMECs and promote HIV-1 attachment and entry. In contrast, the classical entry receptors, CXCR4 and CCR5, only moderately enhanced these processes. HSPGs and CSPGs captured HIV-1 in a gp120-dependent manner. However, no correlation between coreceptor usage and transmigration was identified. Furthermore, brain-derived viruses did not transmigrate more efficiently than lymphoid-derived viruses, suggesting that the ability of HIV-1 to replicate in the brain does not correlate with its capacity to migrate through the BBB as cell-free virus. Given that HIV-1-proteoglycan interactions are based on electrostatic contacts between basic residues in gp120 and sulfate groups in proteoglycans, HIV-1 may exploit these interactions to rapidly enter and migrate through the BBB to invade the brain.

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“…Taken together, it can be concluded that a significant part of NGCs exist in a non-CSPG form. The 220-kDa band may be a dimer of the NGC core protein, because NGC tends to polymerize during preparation or enzymatic digestion (35). The 110-kDa band may be an immature form of NGC with less post-translational modification or a degradation product.…”

Section: Localization Of Cspgs To the Niche Of Neural Stem Cells-mentioning

confidence: 99%

Identification and Functions of Chondroitin Sulfate in the Milieu of Neural Stem Cells

Ida

Shuo

Hirano

et al. 2006

Journal of Biological Chemistry

Self Cite

125

105

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The behavior of cells is generally considered to be regulated by environmental factors, but the molecules in the milieu of neural stem cells have been little studied. We found by immunohistochemistry that chondroitin sulfate (CS) existed in the surroundings of nestin-positive cells or neural stem/progenitor cells in the rat ventricular zone of the telencephalon at embryonic day 14. Brain-specific chondroitin sulfate proteoglycans (CSPGs), including neurocan, phosphacan/receptor-type protein-tyrosine phosphatase ␤, and neuroglycan C, were detected in the ventricular zone. Neurospheres formed by cells from the fetal telencephalon also expressed these CSPGs and NG2 proteoglycan. To examine the structural features and functions of CS polysaccharides in the milieu of neural stem cells, we isolated and purified CS from embryonic day 14 telencephalons. The CS preparation consisted of two fractions differing in size and extent of sulfation: small CS polysaccharides with low sulfation and large CS polysaccharides with high sulfation. Interestingly, both CS polysaccharides and commercial preparations of dermatan sulfate CS-B and an E-type of highly sulfated CS promoted the fibroblast growth factor-2-mediated proliferation of neural stem/progenitor cells. None of these CS preparations promoted the epidermal growth factor-mediated neural stem cell proliferation. These results suggest that these CSPGs are involved in the proliferation of neural stem cells as a group of cell microenvironmental factors.

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Phosphorylation of Neuroglycan C, a Brain-specific Transmembrane Chondroitin Sulfate Proteoglycan, and Its Localization in the Lipid Rafts

Cited by 18 publications

References 60 publications

Cell-Free Human Immunodeficiency Virus Type 1 Transcytosis through Primary Genital Epithelial Cells

Cell-Free Human Immunodeficiency Virus Type 1 Transcytosis through Primary Genital Epithelial Cells

Contribution of Proteoglycans to Human Immunodeficiency Virus Type 1 Brain Invasion

Identification and Functions of Chondroitin Sulfate in the Milieu of Neural Stem Cells

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