Analysis of proteoglycan expression in developing chicken brain: Characterization of a heparan sulfate proteoglycan that interacts with the neural cell adhesion molecule

Burg, Michael A.; Halfter, Willi; Cole, Gregory J.

doi:10.1002/jnr.490410107

Cited by 61 publications

(35 citation statements)

References 69 publications

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“…5a), we assessed whether NCAM expressed on target cells might indirectly exert its inhibitory effect on NK lysis by cis-association with sulfated proteoglycans. 48,49 Our results clearly showed that inhibition of NK lysis was independent of the presence of heparan sulfate, as NCAM transfection of pgsA-745 and CHO-K1 equally reduced the lysis by polyclonal NK cells (Figs. 5b and 5c).…”

Section: Resultsmentioning

confidence: 57%

Blockade of natural killer cell‐mediated lysis by NCAM140 expressed on tumor cells

Jarahian

Watzl

Issa

et al. 2007

Intl Journal of Cancer

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Expression of the neural cell adhesion molecule (NCAM) on malignant cells of neuroendocrine, epithelial and hematopoeitic origin has been reported, but its role for tumor cell recognition by the immune system remained uncertain so far. We have studied the cytotoxicity of the natural killer (NK) cell line NK92 and polyclonal NK cells from different donors, against NCAM-deficient and NCAM-transfected tumors. While the pancreatic carcinoma PANC-1 and the glioblastoma T98G showed no enhanced susceptibility to NK lysis after NCAM transfection, de novo NCAM expression in HeLa cervical carcinoma, SHEP neuroblastoma and the multiple myeloma lines RPMI-8226 and LP-1 was associated with significantly decreased lysis by NK cells. Binding of an NCAM-specific monoclonal antibody to NCAM-positive target cells was able to reverse the reduced lysis susceptibility. Conjugate formation of NCAM-expressing tumor cells with NK cells was blocked and could be restored by anti-NCAM. NK cell-expressed NCAM molecules which might engage in homotypic cis-or trans-interactions had no apparent inhibitory function. The known cis-ligands of NCAM, heparan sulfate proteoglycan and L1-CAM, were also not directly involved in NK inhibition. ICAM-1 mRNA and cell surface expression was downmodulated in NCAM-transfected HeLa cells. ICAM-1 is involved in killer cell immune synapse formation. Its downmodulation may therefore contribute to the reduced lysis of NCAM-expressing target cells. We conclude that aberrant expression of NCAM on tumor cells of different histogenetic origin can lead to inhibition of target cell recognition and lysis by NK cells. ' 2007 Wiley-Liss, Inc.

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Section: Resultsmentioning

confidence: 57%

Blockade of natural killer cell‐mediated lysis by NCAM140 expressed on tumor cells

Jarahian

Watzl

Issa

et al. 2007

Intl Journal of Cancer

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“…However the large width of the synaptic cleft and the interposition of a basal lamina would seem to preclude such homophilic interactions across postnatal NMJs. It seems more likely that NCAM, which postnatally becomes concentrated both prejunctionally and postjunctionally (Covault and Sanes, 1986), would interact heterophilically with other molecules in the synaptic basal lamina, such as neural agrin (Ferns et al, 1993), to which it can bind (Burg et al, 1995). NCAM might also interact with other molecules enriched in synaptic regions including synaptic laminins (Sanes et al, 1990;Patton et al, 1997;Sanes and Lichtman, 1999).…”

Section: Discussionmentioning

confidence: 99%

Structural and Functional Alterations of Neuromuscular Junctions in NCAM-Deficient Mice

2000

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The role of neural cell adhesion molecule (NCAM) in the development and maturation of the neuromuscular junction (NMJ) was explored by characterizing structurally and functionally NMJs from postnatal day 11 (P11) to P30 ϩ/ϩ, ϩ/Ϫ, and Ϫ/Ϫ NCAM null mutant mice. Differences in NCAM levels resulted in alterations in the size and shape of NMJs, with Ϫ/Ϫ NMJs being smaller. Additionally both the withdrawal of polyneuronal innervation and the selective accumulation of synaptic vesicle protein in the presynaptic terminal were delayed. These observations suggest that the bidirectional signaling responsible for these events is impaired at Ϫ/Ϫ NMJs. Functionally, miniature end plate potential size, end plate potential size, and quantal content did not differ from that of wild type under either normal or low release conditions. However at normal release conditions, Ϫ/Ϫ NMJs, unlike ϩ/ϩ NMJs, lacked paired-pulse facilitation. The most striking abnormality was the inability of NCAM null junctions to maintain transmitter output with repetitive stimuli. Combined electrophysiological and FM1-43-labeling studies suggest that NCAM null junctions are unable either to dock or to mobilize a sufficient number of vesicles at high but physiological rates of transmitter release. Taken together our observations show that many aspects of transmission are normal and, thus, that many presynaptic and postsynaptic molecules have assembled properly in the absence of NCAM. However, the fact that NCAM was required for specific aspects of transmission, including pairedpulse facilitation and reliable transmission with repetitive stimuli, suggests that NCAM either is directly involved in these processes or is required for the proper organization and/or function of other molecules underlying these processes. Key words: NCAM; synaptic depression; FM1-43; synapse elimination; neuromuscular transmission; synapse maturationFor proper nervous system function, developing neurons must grow to, and form connections with, their appropriate targets. Subsequent interactions transform these initial connections into highly specialized synapses (for review, see Sanes and Lichtman, 1999). During development of the neuromuscular junction (NMJ), synaptic vesicles that are initially distributed along the length of the motor axon become clustered at presynaptic active zones (Kelly and Zacks, 1969;Lupa and Hall, 1989;Dahm and Landmesser, 1991). Postsynaptically, the density of acetylcholine receptors (AChRs) increases dramatically both by the clustering of diffusely distributed AChRs (Anderson and Cohen, 1977;Frank and Fischbach, 1979;Nitkin et al., 1987) and by transcriptional activation of AChR genes in subsynaptic myonuclei (Usdin and Fischbach, 1986;Fischbach and Rosen, 1997). Postnatally, as the muscle fibers grow, the shape and complexity of the NMJ change, with small uniform plaques of AChRs expanding into pretzel-shaped structures as the nerve terminal grows (Balice-Gordon and Lichtman, 1990). Additionally, there is a withdrawal of all but one motor axon from t...

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“…The HSPG nature of agrin was independently confirmed in two independent studies showing that agrin, when expressed in its entirety, carries heparan sulfate side chains , and showing that a HSPG isolated from bovine kidney comprised agrin-like peptide sequences (Hagen et al, 1993). Brain-derived agrin has also been shown to bind to NCAM via its heparan sulfate side chains, and to promote cell adhesion as an NCAM/ agrin complex (Burg et al, 1995).…”

Section: Indexing Terms: Proteoglycan; Extracellular Matrix; Axonal Gmentioning

confidence: 98%

Distribution and substrate properties of agrin, a heparan sulfate proteoglycan of developing axonal pathways

et al. 1997

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The distribution and substrate properties of agrin, an extracellular matrix heparan sulfate proteoglycan (HSPG), was investigated in the developing chick nervous system by immunocytochemistry, Western blotting, and in neurite outgrowth assays. By comparing the distribution of agrin with that of laminin-1, merosin (laminin-2), neurofilament, and neural cell adhesion molecule (NCAM), it was found that throughout development, agrin is a constituent of all basal laminae. From embryonic day (E) 4 onwards, agrin is also abundant in axonal pathways of the central nervous system, such as the optic nerve, the tectobulbar pathway, the white matter of the spinal cord, and the marginal and the molecular layers of the forebrain and the cerebellum. The abundance of agrin in brain decreases from E13 onwards. In the peripheral nervous system, agrin is present throughout development as a constituent of the Schwann cell basal laminae. Western blots confirmed the immunocytochemical data, showing maximum expression of agrin occurs during the early to medium stages of brain development. Western blots also showed that in mouse and human brain, agrin exists as an HSPG. Purified agrin did not support neurite outgrowth, rather it inhibited retinal neurite extension on mixed agrin/merosin substrates. Despite the fact that agrin, when used as a substrate inhibited neurite outgrowth, its temporal and spatial overlap with growing axons suggests that agrin has a supportive role in the development of axonal pathways, possibly as a binding component for growth factors and cell adhesion proteins.

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Analysis of proteoglycan expression in developing chicken brain: Characterization of a heparan sulfate proteoglycan that interacts with the neural cell adhesion molecule

Cited by 61 publications

References 69 publications

Blockade of natural killer cell‐mediated lysis by NCAM140 expressed on tumor cells

Blockade of natural killer cell‐mediated lysis by NCAM140 expressed on tumor cells

Structural and Functional Alterations of Neuromuscular Junctions in NCAM-Deficient Mice

Distribution and substrate properties of agrin, a heparan sulfate proteoglycan of developing axonal pathways

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