title: Direct evidence that neural cell adhesion molecule (NCAM) polysialylation increases intermembrane repulsion and abrogates adhesion.
abstract: Molecular force measurements quantified the impact of polysialylation on the adhesive properties both of membrane-bound neural cell adhesion molecule (NCAM) and of other proteins on the same membrane. These results show quantitatively that NCAM polysialylation increases the range and magnitude of intermembrane repulsion. The repulsion is sufficient to overwhelm both homophilic NCAM and cadherin attraction at physiological ionic strength, and it abrogates the protein-mediated intermembrane adhesion. The steric repulsion is ionic strength dependent and decreases substantially at high monovalent salt concentrations with a concomitant increase in the intermembrane attraction. The magnitude of the repulsion also depends on the amount of polysialic acid (PSA) on the membranes, and the PSA-dependent attenuation of cadherin adhesion increases with increasing PSA-NCAM:cadherin ratios. These findings agree qualitatively with independent reports based on cell adhesion studies and reveal the likely molecular mechanism by which NCAM polysialylation regulates cell adhesion and intermembrane space.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Illinois 61801, USA.
authors.forename: Colin P
authors.initials: CP
authors.lastname: Johnson
authors.forename: Ichiro
authors.initials: I
authors.lastname: Fujimoto
authors.forename: Urs
authors.initials: U
authors.lastname: Rutishauser
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Leckband
mesh_terms: D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D002645:Chickens; D006224:Cricetinae; D015394:Molecular Structure; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D012794:Sialic Acids / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C021319:polysialic acid