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Bestrophin-2 and glutamine synthetase form a complex for glutamate release.

Owji AP, Yu K, Kittredge A, Wang J, Zhang Y, Yang T
Nature 611 180-187 (2022)
Cited: 4 times
EuropePMC logo PMID: 36289327

Abstract

Bestrophin-2 (BEST2) is a member of the bestrophin family of calcium-activated anion channels that has a critical role in ocular physiology1-4. Here we uncover a directional permeability of BEST2 to glutamate that heavily favours glutamate exit, identify glutamine synthetase (GS) as a binding partner of BEST2 in the ciliary body of the eye, and solve the structure of the BEST2-GS complex. BEST2 reduces cytosolic GS activity by tethering GS to the cell membrane. GS extends the ion conducting pathway of BEST2 through its central cavity and inhibits BEST2 channel function in the absence of intracellular glutamate, but sensitizes BEST2 to intracellular glutamate, which promotes the opening of BEST2 and thus relieves the inhibitory effect of GS. We demonstrate the physiological role of BEST2 in conducting chloride and glutamate and the influence of GS in non-pigmented ciliary epithelial cells. Together, our results reveal a novel mechanism of glutamate release through BEST2-GS.

Articles - 8ecy mentioned but not cited (1)

  1. Bestrophin-2 and glutamine synthetase form a complex for glutamate release. Owji AP, Yu K, Kittredge A, Wang J, Zhang Y, Yang T. Nature 611 180-187 (2022)


Reviews citing this publication (2)

  1. GABA tone regulation and its cognitive functions in the brain. Koh W, Kwak H, Cheong E, Lee CJ. Nat Rev Neurosci 24 523-539 (2023)
  2. Excitotoxic Storms of Ischemic Stroke: A Non-neuronal Perspective. Yang XM, Yu H, Li JX, Li N, Li C, Xu DH, Zhang H, Fang TH, Wang SJ, Yan PY, Han BB. Mol Neurobiol (2024)

Articles citing this publication (1)

  1. Biocompatible aggregation-induced emission active polyphosphate-manganese nanosheets with glutamine synthetase-like activity in excitotoxic nerve cells. Wang J, Zhao X, Tao Y, Wang X, Yan L, Yu K, Hsu Y, Chen Y, Zhao J, Huang Y, Wei W. Nat Commun 15 3534 (2024)


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