期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 93, 期 7, 页码 999-1008出版社
WILEY-BLACKWELL
DOI: 10.1002/jnr.23533
关键词
glutamate transporter; mitochondria; hexokinase
资金
- NINDS [RO1 NS077773]
- NIH [T32 GM008076, F31 NS086255, T32 NS007413]
- Institutional Intellectual and Developmental Disabilities Research Center [P30 HD26979]
The glutamate transporter GLT-1 is the major route for the clearance of extracellular glutamate in the forebrain, and most GLT-1 protein is found in astrocytes. This protein is coupled to the Na+ electrochemical gradient, supporting the active intracellular accumulation of glutamate. We recently used a proteomic approach to identify proteins that may interact with GLT-1 in rat cortex, including the Na+/K+-ATPase, most glycolytic enzymes, and several mitochondrial proteins. We also showed that most GLT-1 puncta (approximate to 70%) are overlapped by mitochondria in astroglial processes in organotypic slices. From this analysis, we proposed that the glycolytic enzyme hexokinase (HK)-1 might physically form a scaffold to link GLT-1 and mitochondria because HK1 is known to interact with the outer mitochondrial membrane protein voltage-dependent anion channel (VDAC). The current study validates the interactions among HK-1, VDAC, and GLT-1 by using forward and reverse immunoprecipitations and provides evidence that a subfraction of HK1 colocalizes with GLT-1 in vivo. A peptide known to disrupt the interaction between HK and VDAC did not disrupt interactions between GLT-1 and several mitochondrial proteins. In parallel experiments, displacement of HK from VDAC reduced GLT-1-mediated glutamate uptake. These results suggest that, although HK1 forms coimmunoprecipitatable complexes with both VDAC and GLT-1, it does not physically link GLT-1 to mitochondrial proteins. However, the interaction of HK1 with VDAC supports GLT-1-mediated transport activity. (c) 2014 Wiley Periodicals, Inc.
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