Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 179, Issue 14, Pages 3612-3627Publisher
WILEY
DOI: 10.1111/bph.15313
Keywords
Cryo‐ EM; delta receptors; glutamate receptors; ionotropic; metabotropic; synaptic plasticity
Categories
Funding
- Wellcome Trust DBT India Alliance [IA/I/13/2/501023]
- Indian Council of Medical Research (ICMR, India) [3/1/3/JRF-2014/HRD]
- SERB [N-PDF/2016/002621]
- University Grants Commission (UGC), India
- DST Inspire Faculty Funds [DST/INSPIRE/04/2017/001906]
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GluD receptors are a subfamily of ionotropic glutamate receptors that play a crucial role in synapse formation, maturation, and maintenance of central nervous system functions. Despite the lack of knowledge about their endogenous ligands, significant discoveries have been made regarding their role in mediating trans-synaptic interactions and their unique non-swapped architecture. Additionally, the prospect of GluD ionotropic activity being regulated by direct interaction with metabotropic glutamate receptors is exciting.
Glutamate delta-1 (GluD1) and delta-2 (GluD2) receptors belong to the orphan GluD subfamily of ionotropic glutamate receptors (iGluRs). GluDs were classified as ionotropic glutamate receptors based on their sequence similarity. Two decades after these GluDs were first cloned they are still considered orphan due to a lack of knowledge of the endogenous ligands that can activate them. Nevertheless, they are crucial for synapse formation, maturation and maintenance of CNS functions, and are implicated in multiple neuronal disorders, including schizophrenia, autism spectrum disorder and depressive disorders. Over the last decade significant discoveries have been made, include role of GluD receptors in mediating trans-synaptic interactions and their unique non-swapped architecture, which is distinct from other ionotropic glutamate receptors. Also, the prospect of GluD ionotropic activity being regulated by direct interaction with metabotropic glutamate receptors is exciting. These discoveries will likely drive the field in the future, providing direction to GluD research.
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