Kiselyov Vladislav V, Soroka Vladislav, Berezin Vladimir, Bock Elisabeth
Protein Laboratory, Institute of Molecular Pathology, Panum Institute, School of Medicine, University of Copenhagen, Blegdamsvej 3C, Building 6.2, Copenhagen, Denmark.
J Neurochem. 2005 Sep;94(5):1169-79. doi: 10.1111/j.1471-4159.2005.03284.x. Epub 2005 Jul 25.
In this review, we analyse the structural basis of the homophilic interactions of the neural cell adhesion molecule (NCAM) and the NCAM-mediated activation of the fibroblast growth factor receptor (FGFR). Recent structural evidence suggests that NCAM molecules form cis-dimers in the cell membrane through a high affinity interaction. These cis-dimers, in turn, mediate low affinity trans-interactions between cells via formation of either one- or two-dimensional 'zippers'. We provide evidence that FGFR is probably activated by NCAM very differently from the way by which it is activated by FGFs, reflecting the different conditions for NCAM-FGFR and FGF-FGFR interactions. The affinity of FGF for FGFR is approximately 10(6) times higher than that of NCAM for FGFR. Moreover, in the brain NCAM is constantly present on the cell surface in a concentration of about 50 microm, whereas FGFs only appear transiently in the extracellular environment and in concentrations in the nanomolar range. We discuss the structural basis for the regulation of NCAM-FGFR interactions by two molecular 'switches', polysialic acid (PSA) and adenosine triphosphate (ATP), which determine whether NCAM acts as a signalling or an adhesion molecule.
在本综述中，我们分析了神经细胞黏附分子（NCAM）的嗜同性相互作用以及NCAM介导的成纤维细胞生长因子受体（FGFR）激活的结构基础。最近的结构证据表明，NCAM分子通过高亲和力相互作用在细胞膜中形成顺式二聚体。这些顺式二聚体进而通过形成一维或二维“拉链”介导细胞间的低亲和力反式相互作用。我们提供的证据表明，NCAM激活FGFR的方式可能与FGF激活FGFR的方式截然不同，这反映了NCAM-FGFR和FGF-FGFR相互作用的不同条件。FGF对FGFR的亲和力比对NCAM对FGFR的亲和力高约10^6倍。此外，在大脑中，NCAM以约50微摩尔的浓度持续存在于细胞表面，而FGF仅在细胞外环境中短暂出现，浓度处于纳摩尔范围内。我们讨论了由两种分子“开关”——多唾液酸（PSA）和三磷酸腺苷（ATP）调控NCAM-FGFR相互作用的结构基础，这两种分子决定了NCAM是作为信号分子还是黏附分子发挥作用。
