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.
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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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