GRID2

Glutamate receptor, ionotropic, delta 2, also known as GluD2, GluRδ2, or δ2, is a is_associated_with::protein that in humans is encoded by the GRID2 is_associated_with::gene.

δ2 proteins are subunits that form excitatory is_associated_with::ligand-gated ion channels and possess 14-24% sequence homology with AMPA, kainate, and NMDA subunits, but, despite their name, do not actually bind is_associated_with::glutamate or various other glutamate agonists. They are considered orphan subunits and their is_associated_with::endogenous is_associated_with::ligand is unknown. δ2-containing receptors are selectively/predominantly expressed in is_associated_with::Purkinje cells in the is_associated_with::cerebellum and play a role in is_associated_with::synaptogenesis, is_associated_with::synaptic plasticity, and is_associated_with::motor coordination, as well as in is_associated_with::apoptosis (see below).

Function
Human glutamate receptor delta-2 (GRID2) is a relatively new member of the family of ionotropic is_associated_with::glutamate receptors which are the predominant excitatory is_associated_with::neurotransmitter receptors in the mammalian brain. GRID2 is a predicted 1,007 amino acid protein that shares 97% identity with the mouse homolog which is expressed selectively in cerebellar is_associated_with::Purkinje cells. A point mutation in mouse GRID2, associated with the phenotype named 'lurcher', in the heterozygous state leads to ataxia and motor coordination deficits resulting from selective, cell-autonomous apoptosis of cerebellar Purkinje cells during postnatal development. Mice homozygous for this mutation die shortly after birth from massive loss of mid- and hindbrain neurons during late is_associated_with::embryogenesis. This strongly suggests a role for GRID2 in neuronal is_associated_with::apoptosis.

Pathology
A heterozygous deletion in GRID2 in humans causes a complicated spastic paraplegia with ataxia, frontotemporal dementia, and lower motor neuron involvement whereas a homozygous beallelic deletion leads to a syndrome of cerebellar ataxia with marked developmental delay, pyramidal tract involvement and tonic upgaze, that can be classified as an ataxia with oculomotor apraxia (AOA).

Ligands
is_associated_with::9-Aminoacridine, is_associated_with::9-tetrahydroaminoacridine, is_associated_with::N1-dansyl-spermine, is_associated_with::N1-dansyl-spermidine, and is_associated_with::pentamidine have been shown to act as antagonists of δ2-containing receptors.

Interactions
GRID2 has been shown to interact with is_associated_with::GOPC, is_associated_with::GRIK2, is_associated_with::PTPN4 and is_associated_with::GRIA1. A possible correlation between GRID2 and the pre-B lymphocyte protein 3 (is_associated_with::VPREB3) has been suggested, due to the apparent importance of B-lymphocytes in the origins of cerebellar Purkinje neurons in humans. Morphological studies conducted in GRID2-knockout mice suggest that GRID2 may be present in lymphocytes as well as in the is_associated_with::adrenal cortex, however further studies must be conducted to confirm these claims.