Promotion of neurite and filopodium formation by CD47: Roles of integrins, Rac, and Cdc42
Promotion of neurite and filopodium formation by CD47: Roles of integrins, Rac, and Cdc42
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DOI：
10.1091/mbc.e04-01-0019
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发表时间：
2004-08-01
影响因子：
3.3
通讯作者：
Matozaki, T
中科院分区：
文献类型：
--
作者：
Miyashita, M;Ohnishi, H;Matozaki, T
轴突在发育过程中的延伸受到许多因素的指导，但负责其调节的信号传导机制在很大程度上仍然未知。我们现在已经研究了跨膜蛋白CD 47在N1 E-115神经母细胞瘤细胞中的作用。CD 47的强制表达诱导神经突和丝状伪足的形成。此外，含有CD 47配体SHPS-1的胞外区的Fc融合蛋白诱导丝状伪足形成，并且这种作用通过CD 47过表达而增强。SHPS-1-Fc还促进由血清剥夺触发的神经突和丝状伪足形成。Rac或Cdc 42的抑制分别优先阻断CD 47诱导的神经突和丝状伪足的形成。CD 47的过表达导致Rac和Cdc 42的激活。CD 47的细胞外区域足以通过强制表达诱导神经突形成，但CD 47的整个结构需要通过SHPS-1-Fc增强丝状伪足形成。CD 47诱导的神经突形成也被整合素β 3亚基的mAb抑制。这些结果表明，SHPS-1与CD 47的相互作用通过激活Rac和Cdc 42促进神经突和丝状伪足的形成，并且含有β 3亚基的整合素参与CD 47对神经突形成的影响。
Axon extension during development is guided by many factors, but the signaling mechanisms responsible for its regulation remain largely unknown. We have now investigated the role of the transmembrane protein CD47 in this process in N1E-115 neuroblastoma cells. Forced expression of CD47 induced the formation of neurites and filopodia. Furthermore, an Fc fusion protein containing the extracellular region of the CD47 ligand SHPS-1 induced filopodium formation, and this effect was enhanced by CD47 overexpression. SHPS-1-Fc also promoted neurite and filopodium formation triggered by serum deprivation. Inhibition of Rac or Cdc42 preferentially blocked CD47-induced formation of neurites and filopodia, respectively. Overexpression of CD47 resulted in the activation of both Rac and Cdc42. The extracellular region of CD47 was sufficient for the induction of neurite formation by forced expression, but the entire structure of CD47 was required for enhancement of filopodium formation by SHPS-1-Fc. Neurite formation induced by CD47 was also inhibited by a mAb to the integrin beta3 subunit. These results indicate that the interaction of SHPS-1 with CD47 promotes neurite and filopodium formation through the activation of Rac and Cdc42, and that integrins containing the beta3 subunit participate in the effect of CD47 on neurite formation.