TY - JOUR

T1 - NCAM regulates cell motility.

AU - Prag, Søren

AU - Lepekhin, Eugene A

AU - Kolkova, Kateryna

AU - Hartmann-Petersen, Rasmus

AU - Kawa, Anna

AU - Walmod, Peter S

AU - Belman, Vadym

AU - Gallagher, Helen C

AU - Berezin, Vladimir

AU - Bock, Elisabeth

AU - Pedersen, Nina

N1 - Keywords: Animals; Binding Sites; Cell Adhesion; Cell Membrane; Cell Movement; Cytoplasm; Extracellular Matrix Proteins; Gene Expression Regulation; Glioma; Heparan Sulfate Proteoglycans; Humans; Integrins; Neural Cell Adhesion Molecules; Protein Isoforms; Protein Structure, Tertiary; Rats; Tumor Cells, Cultured

PY - 2002

Y1 - 2002

N2 - Cell migration is required during development of the nervous system. The regulatory mechanisms for this process, however, are poorly elucidated. We show here that expression of or exposure to the neural cell adhesion molecule (NCAM) strongly affected the motile behaviour of glioma cells independently of homophilic NCAM interactions. Expression of the transmembrane 140 kDa isoform of NCAM (NCAM-140) caused a significant reduction in cellular motility, probably through interference with factors regulating cellular attachment, as NCAM-140-expressing cells exhibited a decreased attachment to a fibronectin substratum compared with NCAM-negative cells. Ectopic expression of the cytoplasmic part of NCAM-140 also inhibited cell motility, presumably via the non-receptor tyrosine kinase p59(fyn) with which NCAM-140 interacts. Furthermore, we showed that the extracellular part of NCAM acted as a paracrine inhibitor of NCAM-negative cell locomotion through a heterophilic interaction with a cell-surface receptor. As we showed that the two N-terminal immunoglobulin modules of NCAM, which are known to bind to heparin, were responsible for this inhibition, we presume that this receptor is a heparan sulfate proteoglycan. A model for the inhibitory effect of NCAM is proposed, which involves competition between NCAM and extracellular components for the binding to membrane-associated heparan sulfate proteoglycan.

AB - Cell migration is required during development of the nervous system. The regulatory mechanisms for this process, however, are poorly elucidated. We show here that expression of or exposure to the neural cell adhesion molecule (NCAM) strongly affected the motile behaviour of glioma cells independently of homophilic NCAM interactions. Expression of the transmembrane 140 kDa isoform of NCAM (NCAM-140) caused a significant reduction in cellular motility, probably through interference with factors regulating cellular attachment, as NCAM-140-expressing cells exhibited a decreased attachment to a fibronectin substratum compared with NCAM-negative cells. Ectopic expression of the cytoplasmic part of NCAM-140 also inhibited cell motility, presumably via the non-receptor tyrosine kinase p59(fyn) with which NCAM-140 interacts. Furthermore, we showed that the extracellular part of NCAM acted as a paracrine inhibitor of NCAM-negative cell locomotion through a heterophilic interaction with a cell-surface receptor. As we showed that the two N-terminal immunoglobulin modules of NCAM, which are known to bind to heparin, were responsible for this inhibition, we presume that this receptor is a heparan sulfate proteoglycan. A model for the inhibitory effect of NCAM is proposed, which involves competition between NCAM and extracellular components for the binding to membrane-associated heparan sulfate proteoglycan.

M3 - Journal article

C2 - 11839780

VL - 115

SP - 283

EP - 292

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - Pt 2

ER -