Molecular mechanisms of NCAM function

Hinsby, Anders M.; Berezin, Vladimir; Bock, Elisabeth

doi:10.2741/1393

Cited by 90 publications

(71 citation statements)

References 179 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 3 major isoforms that arise from alternative splicing contain either a glycosylphosphatidyl inositol anchor (NCAM120) or a transmembrane domain with a short (NCAM140) or long (NCAM180) cytoplasmic tail. 1,2 The ectodomain is heavily N-glycosylated. Predominantly during embryonic development, 2 of the 6 N-glycans can be modified by attachment of long, linear polysialic acid chains that decrease the homophilic adhesive function of NCAM, but also positively modulate heterophilic interactions.…”

mentioning

confidence: 99%

“…Through their cytoplasmic domains, by integration into lipid rafts and through the associated receptor tyrosine kinase FGFR, all NCAM isoforms are engaged in signal transduction pathways mainly converging into MAP kinase activation. [1][2][3] NCAM is abundantly expressed on almost all cells of the nervous system, where it plays a critical role during brain development, mediating adhesion between neural cells, stimulating axonal outgrowth and regulating synaptic plasticity. 4,5 Outside the nervous system, aberrant NCAM/CD56 expression has been noted for several kinds of hematopoietic malignancies and carcinomas.…”

mentioning

confidence: 99%

“…1,2 NCAM belongs to the immunoglobulin (Ig) superfamily of cell adhesion molecules. The ectodomain contains 5 Ig-like modules and 2 fibronectin (FN) type III modules which can be modified by optional insertion of short exons in the original transcript.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

Jarahian

Watzl

Issa

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

Jarahian

Watzl

Issa

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Fas2 and its mammalian ortholog NCAM have been implicated in a variety of processes in neural development and function, such as axon guidance, synaptic development, and plasticity (16). The function of Fas2/ NCAM is tightly controlled to ensure proper development of the nervous system.…”

Section: Discussionmentioning

confidence: 99%

Control of axon–axon attraction by Semaphorin reverse signaling

Hsieh

Chang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Semaphorin family proteins are well-known axon guidance ligands. Recent studies indicate that certain transmembrane Semaphorins can also function as guidance receptors to mediate axon-axon attraction or repulsion. The mechanisms by which Semaphorin reverse signaling modulates axon-surface affinity, however, remain unknown. In this study, we reveal a novel mechanism underlying upregulation of axon-axon attraction by Semaphorin-1a (Sema1a) reverse signaling in the developing Drosophila visual system. Sema1a promotes the phosphorylation and activation of Moesin (Moe), a member of the ezrin/radixin/moesin family of proteins, and downregulates the level of active Rho1 in photoreceptor axons. We propose that Sema1a reverse signaling activates Moe, which in turn upregulates Fas2-mediated axon-axon attraction by inhibiting Rho1.T he Semaphorin family of proteins are well-known axon guidance cues or ligands, which activate their receptors on a variety of axons to control axonal pathfinding, fasciculation, branching, and target selection in vertebrates and invertebrates (1, 2). Recent studies demonstrate that certain transmembrane Semaphorins can also function as a receptor to mediate downstream signaling events in both vertebrates and invertebrates (3-7). For example, we show that the transmembrane Semaphorin1a (Sema1a) functions as an axon guidance receptor for PlexinA (PlexA) in mediating reverse signaling in the developing Drosophila visual system (3, 8). Sema1a reverse signaling promotes photoreceptor (R cell) axon-axon attractions during the establishment of R-cell-to-optic-lobe connections (8). A recent study by Kolodkin and colleagues also demonstrates that Sema1a reverse signaling mediates axon-axon repulsion in Drosophila motor axon guidance (6).To understand the mechanisms underlying upregulation of axon-axon attractions by Sema1a reverse signaling, we set out to examine potential genetic interactions between Sema1a and other genes in R-cell axon guidance. The establishment of R-cell-to-optic-lobe connections in the Drosophila adult visual system begins at the third-instar larval stage (9). At the thirdinstar larval stage, differentiating R cells in the eye-imaginal disk extend axons through the optic stalk into the developing optic lobe. R1-R6 axons terminate at the superficial lamina layer, where their growth cones closely associate with each other at the lamina termination site. R7 and R8 axons bypass the lamina and terminate in the deeper medulla layer.In this study, we present evidence that Sema1a reverse signaling promotes R-cell axon-axon attraction by upregulating the adhesive function of Fasciclin 2 (Fas2). Sema1a interacts genetically and physically with Moesin (Moe), a member of the ezrin/radixin/moesin (ERM) family proteins, and downregulates the level of active Rho1. Our results support that Sema1a-induced reduction in the level of active Rho1 in R-cell axons contributes to an increase in Fas2-mediated R-cell axon-axon attraction. Results Sema1aInteracts with Fas2 in Regulating R-Cell Axonal Projec...

show abstract

“…The neural cell adhesion molecule (NCAM) is a member of the immunoglobulin superfamily and it is found in three major isoforms (Hinsby et al, 2004). The extracellular part of the NCAM consists of five Ig-like domains and two fibronectin Int.…”

Section: Abstract: Ncam Fgfr2 Mouse Pla Developmentmentioning

confidence: 99%

Co-localization of neural cell adhesion molecule and fibroblast growth factor receptor 2 in early embryo development

et al. 2011

View full text Add to dashboard Cite

During development there is a multitude of signaling events governing the assembly of the developing organism. Receptors for signaling molecules such as fibroblast growth factor receptor 2 (FGFR2) enable the embryo to communicate with the surrounding environment and activate downstream pathways. The neural cell adhesion molecule (NCAM) was first characterized as a cell adhesion molecule highly expressed in the nervous system, but recent studies have shown that it is also a signaling receptor. Using a novel single oocyte adaptation of the proximity ligation assay, we here show a close association between NCAM and FGFR2 in mouse oocytes and 2-cell embryos. Real-time PCR analyses revealed the presence of messenger RNA encoding key proteins in downstream signaling pathways in oocytes and early mouse embryos. In summary these findings show a co-localization of NCAM and FGFR2 in early vertebrate development with intracellular signaling pathways present to enable a cellular response. KEY WORDS: NCAM, FGFR2, mouse, PLA, developmentGrowth factors, such as fibroblast growth factors (FGFs) are crucial for the embryo development and the presence of FGF receptors in the developing oocyte have been shown in several vertebrate species (Ben-Haroush et al., 2005, Cailliau et al., 2003, Yoshida et al., 1998. There are four well-characterized FGF receptors (FGFRs 1-4), which contain a single transmembrane domain, an intracellular tyrosine kinase domain, and an extracellular FGF binding domain composed of two or three immunoglobulin (Ig)-like domains. The transcripts encoding FGF receptor 2 (FGFR2) are alternatively spliced to produce two FGFR2 transcripts (FGFR2-1 and FGFR2-2) that translate into two proteins with different carboxy-terminal halves of the Ig-III domain. This domain is determined by the inclusion of either exon IIIb (FGFR2-2) or exon IIIc (FGFR2-1), which controls ligandbinding specificity (Miki et al., 1992).Cell adhesion molecules (CAMs) are cell surface molecules responsible for mediating adhesion of cells to other cells and/or the extracellular matrix. The neural cell adhesion molecule (NCAM) is a member of the immunoglobulin superfamily and it is found in three major isoforms (Hinsby et al., 2004). The extracellular part of the NCAM consists of five Ig-like domains and two fibronectin Int.

show abstract

Molecular mechanisms of NCAM function

Cited by 90 publications

References 179 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

Control of axon–axon attraction by Semaphorin reverse signaling

Co-localization of neural cell adhesion molecule and fibroblast growth factor receptor 2 in early embryo development

Contact Info

Product

Resources

About