Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Science. 2019 Mar 1;363(6430):948-955. doi: 10.1126/science.aat5053.
We investigated the roles of components of neuronal synapses for development of the air sac primordium (ASP). The ASP, an epithelial tube, extends specialized signaling filopodia called cytonemes that take up signals such as Dpp (Decapentaplegic, a homolog of the vertebrate bone morphogenetic protein) from the wing imaginal disc. Dpp signaling in the ASP was compromised if disc cells lacked Synaptobrevin and Synaptotagmin-1 (which function in vesicle transport at neuronal synapses), the glutamate transporter, and a voltage-gated calcium channel, or if ASP cells lacked Synaptotagmin-4 or the glutamate receptor GluRII. Transient elevations of intracellular calcium in ASP cytonemes correlate with signaling activity. Calcium transients in ASP cells depend on GluRII, are activated by l-glutamate and by stimulation of an optogenetic ion channel expressed in the wing disc, and are inhibited by EGTA and by the GluR inhibitor NASPM (1-naphthylacetyl spermine trihydrochloride). Activation of GluRII is essential but not sufficient for signaling. Cytoneme-mediated signaling is glutamatergic.
我们研究了神经元突触成分在气囊原基（ASP）发育中的作用。ASP 是一个上皮管，延伸出专门的信号丝状伪足，称为纤毛，从翅膀 imaginal 盘接收 Dpp（Decapentaplegic，脊椎动物骨形态发生蛋白的同源物）等信号。如果盘细胞缺乏 Synaptobrevin 和 Synaptotagmin-1（在神经元突触的囊泡运输中起作用）、谷氨酸转运体和电压门控钙通道，或者如果 ASP 细胞缺乏 Synaptotagmin-4 或谷氨酸受体 GluRII，Dpp 信号在 ASP 中的作用就会受到损害。ASP 纤毛中的细胞内钙的瞬时升高与信号活性相关。ASP 细胞中的钙瞬变依赖于 GluRII，可被 l-谷氨酸和在翅膀盘表达的光遗传学离子通道的刺激激活，并被 EGTA 和 GluR 抑制剂 NASPM（1-萘乙酰基 spermine 三盐酸盐）抑制。GluRII 的激活对于信号传递是必要的，但不是充分的。纤毛介导的信号传递是谷氨酸能的。
