Hansen Stine M M, Køhler Lene B, Li Shizhong, Kiselyov Vladislav, Christensen Claus, Owczarek Sylwia, Bock Elisabeth, Berezin Vladimir
Protein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
J Neurochem. 2008 Sep;106(5):2030-41. doi: 10.1111/j.1471-4159.2008.05544.x. Epub 2008 Jul 4.
The neural cell adhesion molecule (NCAM) directly interacts with the fibroblast growth factor receptor (FGFR). Both fibronectin type III (FN3) modules of NCAM are involved in this interaction. One of the NCAM-FGFR contact sites has been localized recently to the upper N-terminal part of the second NCAM FN3 module encompassing the F and G beta-strands and the interconnecting loop region. Here, we investigated whether any of the six putative strand-loop-strand regions in the first NCAM FN3 module are involved in FGFR interactions. Peptide sequences encompassing these regions, termed encamins, were synthesized and tested for their ability to bind and activate FGFR. Encamins localized to the N-terminal part of the first FN3 module did not interact with FGFR, whereas encamins localized to the C-terminal part, termed EncaminA, C and E, bound to and activated FGFR. The encamins induced FGFR-dependent neurite outgrowth, and EncaminC and E promoted neuronal survival and enhanced pre-synaptic function. In conclusion, the interaction between NCAM and FGFR probably involves multiple contact sites at an interface formed by the two NCAM FN3 modules and FGFR, and encamins could constitute important pharmacological tools for the study of specific functional aspects of NCAM, including neuroprotection and modulation of plasticity.
神经细胞黏附分子（NCAM）直接与成纤维细胞生长因子受体（FGFR）相互作用。NCAM的两个纤连蛋白III型（FN3）模块均参与了这种相互作用。最近已将NCAM-FGFR接触位点之一定位到第二个NCAM FN3模块的N端上部，该区域包含F和Gβ链以及相互连接的环区。在此，我们研究了第一个NCAM FN3模块中的六个假定的链-环-链区域是否参与FGFR相互作用。合成了包含这些区域的肽序列（称为encamins），并测试了它们结合和激活FGFR的能力。定位于第一个FN3模块N端部分的encamins不与FGFR相互作用，而定位于C端部分的encamins（称为EncaminA、C和E）则与FGFR结合并激活FGFR。encamins诱导了FGFR依赖性神经突生长，EncaminC和E促进了神经元存活并增强了突触前功能。总之，NCAM与FGFR之间的相互作用可能涉及由两个NCAM FN3模块和FGFR形成的界面处的多个接触位点，并且encamins可能构成研究NCAM特定功能方面（包括神经保护和可塑性调节）的重要药理学工具。
