TY - JOUR
T1 - Recognition of the A chain carboxy-terminal heparin binding region of fibronectin involves multiple sites
T2 - Two contiguous sequences act independently to promote neural cell adhesion
AU - Haugen, P. K.
AU - McCarthy, J. B.
AU - Skubitz, A. P.N.
AU - Furcht, L. T.
AU - Letourneau, P. C.
PY - 1990/12
Y1 - 1990/12
N2 - Cellular interactions with fibronectin-treated substrata have a complex molecular basis involving multiple domains. A carboxy-terminal cell and heparin binding region of fibronectin (FN) is particularly interesting because it is a strong promoter of neurite outgrowth (Rogers, S. L., J. B. McCarthy, S. L. Palm, L. T. Furcht, and P. C. Letourneau, 1985. J. Neurosci. 5:369-378) and cell attachment (McCarthy, J. B., S. T. Hagen, and L. T. Furcht. 1986. J. Cell Biol. 102:179-188.). To further understand the molecular mechanisms of neuronal interactions with this region of FN, we screened two peptides from the 33-kD heparin binding fragment of the FN A chain, FNC/H II (KNNQKSEPLIGRKKT) and CS1 (Humphries, M. J., A. Komoriya, S. K. Akiyama, K. Olden, and K. M. Yamada. 1987. J. Biol. Chem. 262:6886-6892), for their ability to promote B104 neuroblastoma cell-substratum adhesion and neurite outgrowth. Both FN-C/H II and CS1 promoted B104 cell attachment in a concentration-dependent and saturable manner, with attachment to FN-C/H II exceeding attachment to CS1. In solution, both exogenous FN-C/H II or CS1 partially inhibited cell adhesion to the 33-kD fragment. Similar results were obtained with anti-FN-C/H II antibodies. In contrast, soluble GRGDSP did not affect B104 cell adhesion to FN-C/H II. These results indicate that both FN-C/H II and CS1 represent distinct, RGD-independent, cell adhesion-promoting sites active within the 33-kD fragment, and further define FN-C/H II as a novel neural recognition sequence in FN. B104 adhesion to FN-C/H II and CS1 differs in sensitivity to heparin, yet each peptide inhibited adhesion to the other peptide, suggesting cell adhesion is somehow related at the cellular level. Within the A chain 33-kD fragment, FN-C/H II and CS1 are contiguous, and might represent components of a larger domain with greater neurite-promoting activity since only the 33-kD fragment, and neither individual peptide, was effective at promoting B104 neurite outgrowth. These data further support the hypothesis that cell responses to FN are mediated by multiple sites involving both heparin-sensitive and -insensitive mechanisms.
AB - Cellular interactions with fibronectin-treated substrata have a complex molecular basis involving multiple domains. A carboxy-terminal cell and heparin binding region of fibronectin (FN) is particularly interesting because it is a strong promoter of neurite outgrowth (Rogers, S. L., J. B. McCarthy, S. L. Palm, L. T. Furcht, and P. C. Letourneau, 1985. J. Neurosci. 5:369-378) and cell attachment (McCarthy, J. B., S. T. Hagen, and L. T. Furcht. 1986. J. Cell Biol. 102:179-188.). To further understand the molecular mechanisms of neuronal interactions with this region of FN, we screened two peptides from the 33-kD heparin binding fragment of the FN A chain, FNC/H II (KNNQKSEPLIGRKKT) and CS1 (Humphries, M. J., A. Komoriya, S. K. Akiyama, K. Olden, and K. M. Yamada. 1987. J. Biol. Chem. 262:6886-6892), for their ability to promote B104 neuroblastoma cell-substratum adhesion and neurite outgrowth. Both FN-C/H II and CS1 promoted B104 cell attachment in a concentration-dependent and saturable manner, with attachment to FN-C/H II exceeding attachment to CS1. In solution, both exogenous FN-C/H II or CS1 partially inhibited cell adhesion to the 33-kD fragment. Similar results were obtained with anti-FN-C/H II antibodies. In contrast, soluble GRGDSP did not affect B104 cell adhesion to FN-C/H II. These results indicate that both FN-C/H II and CS1 represent distinct, RGD-independent, cell adhesion-promoting sites active within the 33-kD fragment, and further define FN-C/H II as a novel neural recognition sequence in FN. B104 adhesion to FN-C/H II and CS1 differs in sensitivity to heparin, yet each peptide inhibited adhesion to the other peptide, suggesting cell adhesion is somehow related at the cellular level. Within the A chain 33-kD fragment, FN-C/H II and CS1 are contiguous, and might represent components of a larger domain with greater neurite-promoting activity since only the 33-kD fragment, and neither individual peptide, was effective at promoting B104 neurite outgrowth. These data further support the hypothesis that cell responses to FN are mediated by multiple sites involving both heparin-sensitive and -insensitive mechanisms.
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M3 - Article
C2 - 2277084
AN - SCOPUS:0025605064
SN - 0021-9525
VL - 111
SP - 2733
EP - 2745
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6 PART 1
ER -