Lactate flux in astrocytes is enhanced by a non-catalytic action of carbonic anhydrase II
Lactate flux in astrocytes is enhanced by a non-catalytic action of carbonic anhydrase II
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DOI：
10.1113/jphysiol.2011.220152
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发表时间：
2012-05-01
影响因子：
5.5
通讯作者：
Becker, Holger M.
中科院分区：
文献类型：
--
作者：
Stridh, Malin H.;Alt, Marco D.;Becker, Holger M.
不同细胞类型之间代谢物的快速交换对于大脑的能量平衡至关重要。除了葡萄糖，乳酸是大脑中的主要代谢物，主要在星形胶质细胞中产生。在本研究中，我们报告，碳酸酐酶2（CAII）增强了流入和流出的乳酸在小鼠小脑星形胶质细胞。乳酸转运的增强是独立的酶的催化活性，但需要直接结合的CAII的C-末端的单羧酸转运蛋白MCT 1，在星形胶质细胞和大多数组织中的主要乳酸/质子共转运蛋白之一。通过采用其分子内质子穿梭，结合到MCT 1的CAII可以充当转运蛋白的“质子收集天线”，抑制转运蛋白孔处质子微区的形成，从而提高乳酸通量。通过这种机制，CAII可以增强星形胶质细胞和神经元之间的乳酸转移，从而为神经元提供更多的能量底物。
Rapid exchange ofmetabolites between different cell types is crucial for energy homeostasis of the brain. Besides glucose, lactate is a major metabolite in the brain and is primarily produced in astrocytes. In the present study, we report that carbonic anhydrase 2 ( CAII) enhances both influx and efflux of lactate in mouse cerebellar astrocytes. The augmentation of lactate transport is independent of the enzyme's catalytic activity, but requires direct binding of CAII to the C-terminal of the monocarboxylate transporter MCT1, one of the major lactate/proton cotransporters in astrocytes and most tissues. By employing its intramolecular proton shuttle, CAII, bound to MCT1, can act as a 'proton collecting antenna' for the transporter, suppressing the formation of proton microdomains at the transporter-pore and thereby enhancing lactate flux. By this mechanism CAII could enhance transfer of lactate between astrocytes and neurons and thus provide the neurons with an increased supply of energy substrate.