The redundancy and diversity between two novel PKC isotypes that regulate learning in Caenorhabditis elegans.
The redundancy and diversity between two novel PKC isotypes that regulate learning in Caenorhabditis elegans.
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调节秀丽隐杆线虫学习的两种新的PKC同型之间的冗余和多样性。
DOI：
10.1073/pnas.2106974119
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发表时间：
2022-01-18
影响因子：
11.1
通讯作者：
Iino Y
中科院分区：
文献类型：
--
作者：
Hiroki S;Iino Y
神经系统可以储存感官刺激的经验。该功能（即，学习）需要一个强大的分子机制，因为准确的信息读出对生存至关重要。在这项研究中，我们发现，实施的味觉学习秀丽隐杆线虫的感觉神经元中的甘油二酯的量可以读出不仅由PKC-1，蛋白激酶C的活性，但也由另一个PKC，TPA-1。由于TPA-1对甘油二酯的敏感性较低，因此在常规学习试验中不起作用。然而，在可能损害系统的条件下，例如老化，TPA-1有助于学习。我们的研究表明，两个PKC实现的学习系统的鲁棒性。秀丽隐杆线虫学习NaCl的浓度，并向先前经历的浓度移动。在这种行为中，NaCl浓度变化的历史反映在味觉感觉神经元ASER中的甘油二酯水平和蛋白激酶C（PKC-1）的活性中，并决定了迁移的方向。在这里，通过遗传筛选，我们发现Gq蛋白的激活弥补了pkc-1功能缺失突变体的行为缺陷。我们发现Gq激活导致ASER感觉神经元中甘油二酯的过度产生，这导致TPA-1的募集，TPA-1是与PKC-1密切相关的nPKC同种型。与pkc-1突变体不同的是，tpa-1的缺失在传统的学习实验中并不明显影响迁移方向。这种差异被认为是由于nPKC同种型的C1和C2样结构域的合作功能。此外，我们研究了tpa-1的补偿能力如何促进学习，发现tpa-1突变体在认知能力下降或环境干扰的背景下学习不那么稳健。这些结果突出了两种nPKC同种型如何有助于学习系统。
The nervous system can store an experience of sensory stimulus. This function (i.e., learning) requires a robust molecular mechanism because accurate readout of information is crucial in survival. In this study, we found that the gustatory learning of Caenorhabditis elegans implemented as the amount of diacylglycerol in the sensory neuron can be read out not only by the activity of PKC-1, a protein kinase C, but also by that of another PKC, TPA-1. Because of its low sensitivity to diacylglycerol, TPA-1 does not function in the conventional learning assay. However, under conditions that may impair the system, such as aging, TPA-1 contributes to the learning. Our study shows the robustness of the learning system achieved by the two PKCs. The nematode Caenorhabditis elegans learns the concentration of NaCl and moves toward the previously experienced concentration. In this behavior, the history of NaCl concentration change is reflected in the level of diacylglycerol and the activity of protein kinase C, PKC-1, in the gustatory sensory neuron ASER and determines the direction of migration. Here, through a genetic screen, we found that the activation of Gq protein compensates for the behavioral defect of the loss-of-function mutant of pkc-1. We found that Gq activation results in hyperproduction of diacylglycerol in ASER sensory neuron, which leads to recruitment of TPA-1, an nPKC isotype closely related to PKC-1. Unlike the pkc-1 mutants, loss of tpa-1 did not obviously affect migration directions in the conventional learning assay. This difference was suggested to be due to cooperative functions of the C1 and C2-like domains of the nPKC isotypes. Furthermore, we investigated how the compensatory capability of tpa-1 contributes to learning and found that learning was less robust in the context of cognitive decline or environmental perturbation in tpa-1 mutants. These results highlight how two nPKC isotypes contribute to the learning system.
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