A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling
A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling
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DOI：
10.1101/gad.1276505
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发表时间：
2005-01-15
影响因子：
10.5
通讯作者：
Bargmann, CI
中科院分区：
文献类型：
--
作者：
Chuang, CF;Bargmann, CI
两个正在发育的秀丽隐杆线虫 AWC 嗅觉神经元之间的随机横向信号相互作用导致它们呈现出不对称的气味受体表达模式，称为 AWC(OFF) 和 AWC(ON)。在这里，我们表明 AWC 横向信号基因 tir-1（以前称为 nsy-2）编码一种保守的突触后蛋白，该蛋白指定 AWC（OFF）和 AWC（ON）之间的选择。遗传证据表明，tir-1 在电压门控钙通道和 CaMKH (UNC-43) 下游发挥作用，通过 NSY-1(ASK1) p38/JNK MAP（丝裂原激活蛋白）激酶级联调节 AWC 不对称性。 TIR-1 将 NSY-1 定位于 AWC 的突触后区域，并且 TIR-1 结合 UNC-43，表明它组装了调节气味受体表达的突触信号复合物。温度变化实验表明，tir-1 在胚胎发生后期的关键时期（接近 AWC 突触形成的时间）影响 AWC。 TIR-1 是一种多结构域蛋白，具有激活信号传导的 TIR（Toll-interleukin-1 受体）结构域、介导轴突突触后区域定位的 SAM 重复结构域和 N 末端抑制结构域。 TIR-1 和其他 TIR 蛋白与脊椎动物和无脊椎动物的先天免疫有关，NSY-1/ASK1 激酶也是如此，因此该通路在免疫信号传导中也可能具有保守的功能。
A stochastic lateral signaling interaction between two developing Caenorhabditis elegans AWC olfactory neurons causes them to take on asymmetric patterns of odorant receptor expression, called AWC(OFF) and AWC(ON). Here we show that the AWC lateral signaling gene tir-1 (previously known as nsy-2) encodes a conserved post-synaptic protein that specifies the choice between AWC(OFF) and AWC(ON). Genetic evidence suggests that tir-1 acts downstream of a voltage-gated calcium channel and CaMKH (UNC-43) to regulate AWC asymmetry via the NSY-1(ASK1) p38/JNK MAP (mitogen-activated protein) kinase cascade. TIR-1 localizes NSY-1 to post-synaptic regions of AWC, and TIR-1 binds UNC-43, suggesting that it assembles a synaptic signaling complex that regulates odorant receptor expression. Temperature-shift experiments indicate that tir-1 affects AWC during a critical period late in embryogenesis, near the time of AWC synapse formation. TIR-1 is a multidomain protein with a TIR (Toll-interleukin-1 receptor) domain that activates signaling, SAM repeats that mediate localization to post-synaptic regions of axons, and an N-terminal inhibitory domain. TIR-1 and other TIR proteins are implicated in vertebrate and invertebrate innate immunity, as are NSY-1/ASK1 kinases, so this pathway may also have a conserved function in immune signaling.