Kulahin Nikolaj, Li Shizhong, Hinsby Anders, Kiselyov Vladislav, Berezin Vladimir, Bock Elisabeth
Protein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Mol Cell Neurosci. 2008 Mar;37(3):528-36. doi: 10.1016/j.mcn.2007.12.001. Epub 2007 Dec 14.
The neuronal cell adhesion molecule (CAM) L1 promotes axonal outgrowth, presumably through an interaction with the fibroblast growth factor receptor (FGFR). The present study demonstrates a direct interaction between L1 fibronectin type III (FN3) modules I-V and FGFR1 immunoglobulin (Ig) modules II and III by surface plasmon resonance analysis. Binding of L1 to FGFR1 was enhanced by adenosine 5'-triphosphate (ATP), adenylylmethylenediphosphonate (AMP-PCP), and guanosine-5'-triphosphate (GTP), but not adenosine monophosphate (AMP). The L1-FN3 modules were capable of activating FGFR1, reflected by receptor phosphorylation, and this resulted in the induction of differentiation of primary neurons, reflected by neurite outgrowth. Furthermore, ATP modulated L1-induced neuronal differentiation and FGFR1 phosphorylation through regulation of the L1-FGFR1 interaction.
神经元细胞黏附分子（CAM）L1可能通过与成纤维细胞生长因子受体（FGFR）相互作用来促进轴突生长。本研究通过表面等离子体共振分析证明了L1纤连蛋白III型（FN3）结构域I-V与FGFR1免疫球蛋白（Ig）结构域II和III之间存在直接相互作用。L1与FGFR1的结合可被三磷酸腺苷（ATP）、腺苷亚甲基二磷酸（AMP-PCP）和三磷酸鸟苷（GTP）增强，但不能被一磷酸腺苷（AMP）增强。L1-FN3结构域能够激活FGFR1，表现为受体磷酸化，这导致原代神经元分化，表现为神经突生长。此外，ATP通过调节L1-FGFR1相互作用来调节L1诱导的神经元分化和FGFR1磷酸化。
