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

iScience

Jack H. Howden¹  James Drew¹  Sana Al Awabdh¹  Hélène Marie¹  Josef T. Kittler¹  Swati Gupta¹  Narges Bazargani¹  David Attwell¹  Souvik Modi¹ 

[1] Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, WC1E 6BT London, UK;

关键词: Molecular biology;    Molecular neuroscience;    Cellular neuroscience;    Cell biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown