Tyrosine and serine phosphorylation of the neural cell adhesion molecule L1 is implicated in its oligomannosidic glycan dependent association with NCAM and neurite outgrowth

Heiland, Petra C.; Griffith, Lee S.; Lange, Rita; Schachner, Melitta; Hertlein, Birgit; Traub, Otto; Schmitz, Brigitte

doi:10.1016/s0171-9335(98)80052-6

Cited by 45 publications

(26 citation statements)

References 58 publications

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“…50,51 To analyze the function of L1-CAM, 2 variant lines of 293 that constitutively express low or intermediate levels of L1-CAM were studied together with 293 cells that overexpress L1-CAM following cDNA transfection (Fig. 6a).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, a potential role of the L1-CAM adhesion molecules, which interacts with NCAM in cis, 50,51 was studied in first experiments. Our experiments using L1-transfected 293 cells clearly suggest that L1-CAM has a stimulating effect on NK cell lysis (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…After a 1 min centrifugation at 1,000 rpm, plates were incubated for 4 hr at 37°C. The supernatant was harvested and 51 Cr release was measured in a g counter. Percent specific release was calculated as ((experimental release-spontaneous release)/(maximum release-spontaneous release)) 3 100.…”

Section: Nk Cell Cytotoxicity Assaymentioning

confidence: 99%

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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: 99%

Section: Discussionmentioning

confidence: 99%

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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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“…It is also conceivable that binding of CD24 to L1 leads to a conformational change or to a steric hindrance of homophilic binding of L1 to the six immunoglobulin-like domains of L1 that comprise the decisive domains for cell binding and neurite outgrowth (32). That carbohydrates may be important for protein-protein interaction has been proposed for P0 (33) or L1-NCAM interactions (11,34). A striking dependence of glycans in trans-interactions has recently been reported for notch, which interacts with its ligands delta and jagged/serrate.…”

Section: Discussionmentioning

confidence: 99%

The Neural Recognition Molecule L1 Is a Sialic Acid-binding Lectin for CD24, Which Induces Promotion and Inhibition of Neurite Outgrowth

Kleene

Yang

Kutsche

et al. 2001

Journal of Biological Chemistry

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117

113

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Among the recognition molecules that determine a neuron's interaction with other cells, L1 and CD24 have been suggested to cooperate with each other in neurite outgrowth and signal transduction. Here we report that binding of CD24 to L1 depends on ␣2,3-sialic acid on CD24, which determines the CD24 induced and cell typespecific promotion or inhibition of neurite outgrowth. Using knockout mutants, we could show that the CD24-induced effects on neurite outgrowth are mediated via L1, and not GPI-linked CD24, by trans-interaction of L1 with sialylated CD24. This glycoform is excluded together with L1 from raft microdomains, suggesting that molecular compartmentation in the surface membrane could play a role in signal transduction.Path-finding of growth cones and neurite outgrowth toward targets are important events in the developing and regenerating nervous system and in synaptic remodeling during learning and memory. Axonal guidance depends on molecules at the cell surface and in the extracellular matrix. The different and often changing combinations of molecularly associated recognition molecules at the cell surface are important determinants of the ways by which the cell surface communicates with the cell interior, where cell surface signals are integrated to influence cell behavior.Two recognition molecules, L1 of the immunoglobulin superfamily and CD24, a highly glycosylated mucin type glycoprotein, interact with each other functionally (1, 2). L1 is a 200-kDa homophilic and heterophilic adhesion molecule expressed by many postmitotic neurons in the central nervous system (for reviews, see Refs. 3 and 4). It is one of the most potent promoters of neurite outgrowth in vitro known so far. Mutants of L1 in mice and men strongly underscore its importance during embryonic development in vivo (3,5,6).CD24 is linked to the surface membrane by a glycosyl phosphatidylinositol anchor and is, therefore, unable to directly interact with cytoplasmic proteins. It is also known as heatstable antigen or nectadrin with a peptide core of only 30 amino acids (for references, see Ref. 1). Similar to L1, it is highly expressed by neurons (7,8). The apparent molecular weight of CD24 varies considerably among cell types and also within each cell type, depending on its developmental stage due to differences in glycosylation pattern (for references, see Refs. 1 and 7). These observations suggest that post-translational modifications of CD24 play an important functional role. CD24 acts as a co-stimulator for various physiological functions. In the nervous system, CD24 has been reported to interact with L1 to stimulate cell adhesion and to increase intracellular Ca 2ϩ levels (1, 2). Interestingly, CD24 has been shown to inhibit neurite outgrowth of neonatal retinal ganglion cells and dorsal root ganglion neurons in culture (8) by yet unknown signal transduction mechanisms.Based on these observations on the functional interplay and molecular association between L1 and CD24, we decided to further study their functional interdependence. Her...

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“…Since synapsin is released from astrocytes via exosomes and promotes neurite outgrowth in an oligomannose-dependent manner, it is likely that the binding of the extracellular glial-derived oligomannose-bearing synapsin to neuronal oligomannose-binding cell surface receptors may trigger neurite outgrowth. NCAM is an oligomannose-binding neuronal protein involved in neurite outgrowth (Horstkorte et al, 1993;Heiland et al, 1998) and thus is a prime candidate to interact with synapsin in an oligomannose-dependent manner. First, we investigated by ELISA whether NCAM binds to synapsin using NCAM-Fc, and CHL1-Fc as negative control.…”

Section: Synapsin Is Released From Glial-derived Exosomes and Is Neurmentioning

confidence: 99%

Synapsin I Is an Oligomannose-Carrying Glycoprotein, Acts As an Oligomannose-Binding Lectin, and Promotes Neurite Outgrowth and Neuronal Survival When Released via Glia-Derived Exosomes

Wang¹,

Cesca²,

Loers³

et al. 2011

J. Neurosci.

269

201

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Tyrosine and serine phosphorylation of the neural cell adhesion molecule L1 is implicated in its oligomannosidic glycan dependent association with NCAM and neurite outgrowth

Cited by 45 publications

References 58 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

The Neural Recognition Molecule L1 Is a Sialic Acid-binding Lectin for CD24, Which Induces Promotion and Inhibition of Neurite Outgrowth

Synapsin I Is an Oligomannose-Carrying Glycoprotein, Acts As an Oligomannose-Binding Lectin, and Promotes Neurite Outgrowth and Neuronal Survival When Released via Glia-Derived Exosomes

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