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The non-adrenergic imidazoline-1 receptor protein nischarin is a key regulator of astrocyte glutamate uptake

Gupta, Swati; Bazargani, Narges; Drew, James; Howden, Jack; Modi, Souvik; Al Awabdh, Sana; Marie, Hélène; ... Kittler, Josef T; + view all (2022) The non-adrenergic imidazoline-1 receptor protein nischarin is a key regulator of astrocyte glutamate uptake. iScience , 25 (4) , Article 104127. 10.1016/j.isci.2022.104127. Green open access

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Abstract

Astrocytic GLT-1 is the main glutamate transporter involved in glutamate buffering in the brain, pivotal for glutamate removal at excitatory synapses to terminate neurotransmission and for preventing excitotoxicity. We show here that the surface expression and function of GLT-1 can be rapidly modulated through the interaction of its N-terminus with the nonadrenergic imidazoline-1 receptor protein, Nischarin. The phox domain of Nischarin is critical for interaction and internalization of surface GLT-1. Using live super-resolution imaging, we found that glutamate accelerated Nischarin-GLT-1 internalization into endosomal structures. The surface GLT-1 level increased in Nischarin knockout astrocytes, and this correlated with a significant increase in transporter uptake current. In addition, Nischarin knockout in astrocytes is neuroprotective against glutamate excitotoxicity. These data provide new molecular insights into regulation of GLT-1 surface level and function and suggest new drug targets for the treatment of neurological disorders.

Type: Article
Title: The non-adrenergic imidazoline-1 receptor protein nischarin is a key regulator of astrocyte glutamate uptake
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.isci.2022.104127
Publisher version: https://doi.org/10.1016/j.isci.2022.104127
Language: English
Additional information: Copyright © 2022 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Molecular biology, Molecular neuroscience, Cellular neuroscience, Cell biology
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10146624
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