Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes alpha7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons.
Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes alpha7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons.
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DOI：
10.1523/jneurosci.2271-09.2009
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发表时间：
2009-11-25
期刊：
影响因子：
--
通讯作者：
Nishi R
中科院分区：
文献类型：
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作者：
Hruska M;Keefe J;Wert D;Tekinay AB;Hulce JJ;Ibañez-Tallon I;Nishi R
Ly-6超家族的脊椎动物α-银环蛇毒素样分子被认为是成体神经系统中活性和存活的平衡者。为了确定该家族的成员是否参与了禽类睫状神经节的发育，我们通过与小鼠lynx 1和lynx 2的结构同源性鉴定了6个鸡基因。其中一个基因是前列腺干细胞抗原（PSCA）的直系同源基因，在胚胎第8天（睫状神经节神经元细胞丢失之前）几乎检测不到，但随着神经元数量在E9和E14之间开始下降，该基因增加了100倍以上。PSCA在鸡和小鼠端脑和外周神经节中高度表达，并与含α7烟碱乙酰胆碱受体（α7-nAChRs）的表达相关。睫状神经节中细胞死亡前错误表达PSCA阻断尼古丁对α7-nAChR的激活，并挽救脉络膜亚群免于死亡。因此，PSCA，一种先前被鉴定为前列腺癌标志物的分子，是神经系统中Ly-6神经毒素样家族的成员，并且可能在发育期间作为α7信号传导诱导的细胞死亡的调节剂发挥作用。
Vertebrate α–bungarotoxin-like molecules of the Ly-6 super family have been implicated as balancers of activity and survival in the adult nervous system. To determine whether a member of this family could be involved in the development of the avian ciliary ganglion, we identified 6 Gallus genes by their homology in structure to mouse lynx1 and lynx2. One of these genes, an ortholog of prostate stem cell antigen (PSCA), is barely detectable at embryonic day 8, prior to neuronal cell loss in the ciliary ganglion, but increases over 100-fold as the number of neurons begins to decline between E9 and E14. PSCA is highly expressed in chicken and mouse telencephalon and peripheral ganglia and correlates with expression of α7-containing nicotinic acetylcholine receptors (α7-nAChRs). Misexpressing PSCA prior to cell death in the ciliary ganglion blocks α7-nAChR activation by nicotine and rescues the choroid subpopulation from dying. Thus, PSCA, a molecule previously identified as a marker of prostate cancer, is a member of the Ly-6 neurotoxin-like family in the nervous system, and is likely to play a role as a modulator of α7 signaling induced cell death during development.