Paquin Nicolas, Murata Yasunobu, Froehlich Allan, Omura Daniel T, Ailion Michael, Pender Corinne L, Constantine-Paton Martha, Horvitz H Robert
Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Curr Biol. 2016 Apr 4;26(7):862-71. doi: 10.1016/j.cub.2016.01.049. Epub 2016 Mar 3.
The modification of behavior in response to experience is crucial for animals to adapt to environmental changes. Although factors such as neuropeptides and hormones are known to function in the switch between alternative behavioral states, the mechanisms by which these factors transduce, store, retrieve, and integrate environmental signals to regulate behavior are poorly understood. The rate of locomotion of the nematode Caenorhabditis elegans depends on both current and past food availability. Specifically, C. elegans slows its locomotion when it encounters food, and animals in a food-deprived state slow even more than animals in a well-fed state. The slowing responses of well-fed and food-deprived animals in the presence of food represent distinct behavioral states, as they are controlled by different sets of genes, neurotransmitters, and neurons. Here we describe an evolutionarily conserved C. elegans protein, VPS-50, that is required for animals to assume the well-fed behavioral state. Both VPS-50 and its murine homolog mVPS50 are expressed in neurons, are associated with synaptic and dense-core vesicles, and control vesicle acidification and hence synaptic function, likely through regulation of the assembly of the V-ATPase complex. We propose that dense-core vesicle acidification controlled by the evolutionarily conserved protein VPS-50/mVPS50 affects behavioral state by modulating neuropeptide levels and presynaptic neuronal function in both C. elegans and mammals.
行为随经验而改变对于动物适应环境变化至关重要。尽管已知神经肽和激素等因素在交替行为状态之间的转换中起作用，但对于这些因素如何转导、存储、检索和整合环境信号以调节行为的机制却知之甚少。线虫秀丽隐杆线虫的运动速度取决于当前和过去的食物供应情况。具体而言，秀丽隐杆线虫在遇到食物时会减慢其运动速度，并且处于食物匮乏状态的动物比处于饱腹状态的动物减慢得更多。在有食物的情况下，饱腹和食物匮乏动物的减慢反应代表了不同的行为状态，因为它们受不同的基因、神经递质和神经元控制。在这里，我们描述了一种进化上保守的秀丽隐杆线虫蛋白VPS - 50，动物要呈现饱腹行为状态需要该蛋白。VPS - 50及其小鼠同源物mVPS50均在神经元中表达，与突触囊泡和致密核心囊泡相关，并控制囊泡酸化，从而控制突触功能，可能是通过调节V - ATP酶复合体的组装来实现的。我们提出，由进化上保守的蛋白VPS - 50/mVPS50控制的致密核心囊泡酸化通过调节秀丽隐杆线虫和哺乳动物体内的神经肽水平和突触前神经元功能来影响行为状态。
