Neuronal differentiation and activin signal transduction

点击翻译按钮获取中文摘要

The present study was conducted to understand a role of follistatin (FS), an activin-binding protein, in neural induction.The interaction between activin type I and type II receptors is necessary for activin signal transduction. We found that FS can neutralize bioactivity by interference with binding of activin to all known activin type II receptors, rather than that FS inhibits the binding of the type I receptor to the activin/activin type II receptor complex.There are two types of FS : FS-288 and FS-315. FS-288 exhibits high affinity for cell surface heparan sulfate, whereas FS-315 shows low affinity. The present study demonstrated that cell-associated FS-288 accelerates the uptake of activin into cells, leading to increased degradation by lysosomal enzymes, and thus plays a role in the activin clearance system. Furthermore, the cellular internalization and degradation of activin via FS-288 bound to cell surface was also observed when in the presence of FS-288, activin was incubated with animal cap cells from Xenopus embryos. Expression of FS-288 mRNA in developing Xenopus embryos was restricted to the neurula and later stages. These results suggest that the endocytotic degradation of activin must occur at an early stage of neural differntiation in Xenopus embryos to remove the activin signal from cell surfaces.We identified a novel type II activin receptor, II A-N,the expression of which was induced during the neural differentiation of mouse P19 embryonal carcinoma cells (P19 cells). The induction of II A-N mRNA occurred predominantly in conjunction with neural differentiation. II A-N was found to have a 24 bp insertion in the juxtamembrane region of the activin receptor type II A.In vivo expression of II A-N mRNA was detected only in the neural tissues such as brain and spinal cord in adult mouse.