Roosterman Dirk, Cottrell Graeme S
Ruhr Universität Bochum, LWL-Hospital of Psychiatry, Bochum, Germany.
School of Pharmacy, University of Reading, Reading, RG6 6AP, UK.
AIMS Neurosci. 2020 Apr 20;7(2):94-106. doi: 10.3934/Neuroscience.2020007. eCollection 2020.
Since formulation of the Astrocyte-Neuron Lactate Shuttle (ANLS) hypothesis in 1994, the hypothesis has provoked criticism and debate. Our review does not criticise, but rather integrates experimental data characterizing proton-linked monocarboxylate transporters (MCTs) into the ANLS. MCTs have wide substrate specificity and are discussed to be in protein complex with a proton donor (PD). We particularly focus on the proton-driven transfer of l-lactic acid (l-lacH) and pyruvic acid (pyrH), were PDs link MCTs to a flow of energy. The precise nature of the PD predicts the activity and catalytic direction of MCTs. By doing so, we postulate that the MCT4·phosphoglycerate kinase complex exports and at the same time in the same astrocyte, MCT1·carbonic anhydrase II complex imports monocarboxylic acids. Similarly, neuronal MCT2 preferentially imports pyrH. The repertoire of MCTs in astrocytes and neurons allows them to communicate via monocarboxylic acids. A change in imported pyrH/l-lacH ratio in favour of l-lacH encodes signals stabilizing the transit of glucose from astrocytes to neurons. The presented astrocyte neuron communication hypothesis has the potential to unite the community by suggesting that the exchange of monocarboxylic acids paves the path of glucose provision.
自1994年星形胶质细胞-神经元乳酸穿梭（ANLS）假说提出以来，该假说引发了批评和争论。我们的综述并非批评，而是将表征质子偶联单羧酸转运体（MCTs）的实验数据整合到ANLS中。MCTs具有广泛的底物特异性，并且被认为与质子供体（PD）形成蛋白复合物。我们特别关注质子驱动的L-乳酸（L-lacH）和丙酮酸（pyrH）的转运，其中PD将MCTs与能量流联系起来。PD的精确性质决定了MCTs的活性和催化方向。通过这样做，我们推测在同一星形胶质细胞中，MCT4·磷酸甘油酸激酶复合物输出，同时MCT1·碳酸酐酶II复合物输入单羧酸。同样，神经元中的MCT2优先输入pyrH。星形胶质细胞和神经元中MCTs的组成使其能够通过单羧酸进行通讯。导入的pyrH/L-lacH比值向有利于L-lacH的方向变化，编码了稳定葡萄糖从星形胶质细胞向神经元转运的信号。提出的星形胶质细胞-神经元通讯假说有可能通过表明单羧酸的交换为葡萄糖供应铺平道路，从而团结该领域的研究人员。
