Roles for class IIA phosphatidylinositol transfer protein in neurotransmission and behavioral plasticity at the sensory neuron synapses of Caenorhabditis elegans

Roles for class IIA phosphatidylinositol transfer protein in neurotransmission and behavioral plasticity at the sensory neuron synapses of Caenorhabditis elegans
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DOI:
10.1073/pnas.1016232108
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发表时间:
2011-05-03
影响因子:
11.1
通讯作者:
Iino, Yuichi
Iino, Yuichi
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Iwata, Ryo;Oda, Shigekazu;Iino, Yuichi

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越来越多的证据表明,感觉神经元突触不仅传递,而且积极编码感觉信息并将其传递到中枢神经系统。秀丽隐杆线虫的化学感受偏好,表现在趋化性的方向上,在感觉神经元水平上受到先前经验的可逆调节;吸引驱动由二酰基甘油(DAG)信号促进,而抵消排斥驱动需要PtdIns(3,4,5)P(3)信号。在这里,我们报告说,这两个相反的驱动器需要一个IIA类磷脂酰肌醇转移蛋白(PITP),PITP-1,它定位于感觉神经元突触。在pitp-1突变体中,对盐的吸引行为减少,而对盐的条件排斥被消除:突变体明显地显示出对盐的弱吸引行为,而不管先前的经验。为了产生灵活的行为输出,吸引和排斥,PITP-1在味觉神经元ASER中起作用,并可能调节来自ASER的神经传递,因为pitp-1突变不会影响ASER对感觉刺激的Ca(2+)反应。此外,完全吸引盐恢复在pitp-1突变体的磷脂酰肌醇转移结构域单独的表达,也由DGK基因的突变,导致DAG的积累,表明PITP-1通过磷脂酰肌醇运输DAG生产服务,因此,调节突触传递。除了味觉行为外,嗅觉行为和渗透回避也受到检测每个感觉刺激的感觉神经元中的PITP-1的调节。因此,PITP-1依赖性磷脂酰肌醇转运是感觉神经元突触将感觉输入耦合到有效行为反应所必需的。
Growing evidence suggests that sensory neuron synapses not merely pass, but actively encode sensory information and convey it to the central nervous system. The chemosensory preferences of Caenorhabditis elegans, as manifested in the direction of chemotaxis, are reversibly regulated by prior experience at the level of sensory neurons; the attractive drive is promoted by diacylglycerol (DAG) signaling, whereas the counteracting repulsive drive requires PtdIns(3,4,5)P(3) signaling. Here we report that the two opposing drives require a class IIA phosphatidylinositol transfer protein (PITP), PITP-1, which localizes to the sensory neuron synapses. In pitp-1 mutants, attraction behavior to salt is reduced, whereas conditioned repulsion from salt is eliminated: the mutants inflexibly show weak attraction behavior to salt, irrespective of prior experience. To generate flexible behavioral outputs, attraction and repulsion, PITP-1 acts in the gustatory neuron ASER and likely regulates neurotransmission from ASER, as pitp-1 mutations do not affect the ASER Ca(2+) response to sensory stimulus. Furthermore, full attraction to salt is restored in pitp-1 mutants by expression of the phosphatidylinositol transfer domain alone, and also by mutations of a DGK gene that cause accumulation of DAG, suggesting that PITP-1 serves for DAG production via phosphatidylinositol transport and, hence, regulates synaptic transmission. In addition to gustatory behavior, olfactory behaviors and osmotic avoidance are also regulated by PITP-1 in the sensory neurons that detect each sensory stimulus. Thus, PITP-1-dependent phosphatidylinositol transport is essential for sensory neuron synapses to couple sensory inputs to effective behavioral responses.