Kurosawa N, Chen G Y, Kadomatsu K, Ikematsu S, Sakuma S, Muramatsu T
Department of Biochemistry, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Japan.
Glycoconj J. 2001 Jun;18(6):499-507. doi: 10.1023/a:1016042303253.
Cell-surface heparan sulfate proteoglycans participate in molecular events that regulate cell adhesion, migration, and proliferation. The present study was performed to elucidate whether glypican-2 plays a role in interactions of neurons with midkine (MK), a heparin-binding neuroregulatory factor. MK bound to heparan sulfate chains of glypican-2 in a manner similar to syndecan-3. Microbeads coated with MK or poly-L-lysine induced clustering of glypican-2 as well as syndecan-3. Substratum-bound MK or poly-L-lysine induced cell adhesion of N2a neuroblastoma cells, while only MK promoted neurite outgrowth of these cells. Ligation of cell-surface glypican-2 with MK or an antibody against epitope-tagged glypican-2 induced cell adhesion and promoted neurite outgrowth. These results verified that cell-surface glypican-2 bound to MK and suggested that MK-glypican-2 interactions participate in neuronal cell migration and neurite outgrowth. In addition, we observed different localization of epitope-tagged glypican-2 and syndecan-3 on the surface of N2a cells; the result suggested that they may play different roles in MK-mediated neural function.
细胞表面硫酸乙酰肝素蛋白聚糖参与调节细胞黏附、迁移和增殖的分子事件。本研究旨在阐明磷脂酰肌醇蛋白聚糖-2是否在神经元与中期因子（MK，一种肝素结合神经调节因子）的相互作用中发挥作用。MK以类似于syndecan-3的方式与磷脂酰肌醇蛋白聚糖-2的硫酸乙酰肝素链结合。包被有MK或聚-L-赖氨酸的微珠诱导了磷脂酰肌醇蛋白聚糖-2以及syndecan-3的聚集。基质结合的MK或聚-L-赖氨酸诱导了N2a神经母细胞瘤细胞的黏附，而只有MK促进了这些细胞的神经突生长。用MK或抗表位标记的磷脂酰肌醇蛋白聚糖-2抗体连接细胞表面的磷脂酰肌醇蛋白聚糖-2可诱导细胞黏附并促进神经突生长。这些结果证实细胞表面的磷脂酰肌醇蛋白聚糖-2与MK结合，并表明MK-磷脂酰肌醇蛋白聚糖-2相互作用参与神经元细胞迁移和神经突生长。此外，我们观察到表位标记的磷脂酰肌醇蛋白聚糖-2和syndecan-3在N2a细胞表面的定位不同；结果表明它们可能在MK介导的神经功能中发挥不同作用。
