Regulation of cell adhesion by polysialic acid. Effects on cadherin, immunoglobulin cell adhesion molecule, and integrin function and independence from neural cell adhesion molecule binding or signaling activity.
The polysialylation of neural cell adhesion molecule (NCAM) evolved in vertebrates to carry out biological functions related to changes in cell position and morphology. Many of these effects involve the attenuation of cell interactions that are not mediated through NCAM's own adhesion properties. A proposed mechanism for this global effect on cell interaction is the steric inhibition of membrane-membrane apposition based solely on polysialic acid (PSA) biophysical properties. However, it remains possible that the intrinsic binding or signaling properties of the NCAM polypeptide are also involved. To help resolve this issue, this study uses a quantitative cell detachment assay together with cells engineered to display different adhesion receptors together with a variety of polysialylated NCAM polypeptide isoforms and functional domain deletion mutations. The results obtained indicate that regulation by PSA occurs with adhesion receptors as diverse as an IgCAM, a cadherin and an integrin, and does not require NCAM functional domains other than those minimally required for polysialylation. These findings are most consistent with the cell apposition mechanism for PSA action, as this model predicts that the inhibitory effects of PSA-NCAM on cell adhesion should be independent of the nature of the adhesion system and of any intrinsic binding or signaling properties of the NCAM polypeptide itself.
Fujimoto
I
I
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Bruses
J L
JL
Rutishauser
U
U
D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D006224:Cricetinae; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000502:physiology*; D016023:Integrins / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D012794:Sialic Acids / Q000502:physiology*; D012799:Sialyltransferases / Q000235:genetics; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D015820:Cadherins; D007136:Immunoglobulins; D016023:Integrins; D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C021319:polysialic acid; D012799:Sialyltransferases