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FLASH GENE
Symbol GRID2 contributors: mct - updated : 18-10-2016
HGNC name glutamate receptor, ionotropic, delta 2
HGNC id 4576
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal domain (NTD) interacts with presynaptic neurexins (NRXNs) through cerebellin 1 precursor protein (CBLN1) , and is necessary and sufficient for the function of GLUD2 in the regulation of parallel fiber-Purkinje cell synaptogenesis
  • E2 region that is necessary, and also sufficient, to inhibit endocytosis of the receptor from postsynaptic membranes
  • C-terminal region containing at least three domains for protein-protein interactions (ZO1-binding domain at the C terminal, named as the T site, interacts with several postsynaptic density proteins)
    • HOMOLOGY
    interspecies homolog to murine Grid2
    Homologene
    FAMILY
  • glutamate-gated ion channel family
  • ionotropic glutamate receptor family
    • CATEGORY receptor membrane , transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
    text
  • co-localizes with the GRID2 subunit at the Purkinje cell-parallel fiber synapses
  • predominantly expressed on postsynaptic sites at parallel fiber (PF)-Purkinje cell synapses in the cerebellum
    • basic FUNCTION
  • postsynaptic GRID2 is a key regulator of the presynaptic active zone and postsynaptic density organization at parallel fiber-Purkinje cell synapses in the adult brain
  • presence of GRID2 plays an important role in controlling cerebellar functioning
  • excitatory neurotransmitter receptors playing an important role in cerebellar long-term depression, motor learning, motor coordination and synapse development
  • BCL2L2 and GRID2 are two critical proteins acting in distinct pathways to regulate mitochondrial morphogenesis and control Purkinje cell dendrite development and synapse formation
  • differently regulates parallel fiber synaptogenesis and cerebellar long-term depression (LTD) through the extracellular N-terminal domain and the cytoplasmic C-terminal end, respectively
  • essential for cerebellar synapse formation
  • potentially mediates cerebellar synapse formation by interacting with presynaptic NRXNs through CBLN1
  • is part of the GRM11 signaling complex needed for cerebellar synaptic function and motor coordination
  • novel functional role of GRID2 in the retina
  • possible role for GRID2 as possible phenotype modifier in MVKD patients, especially in those with severe phenotypes
  • can be a suppressor in TNF-induced neurodegeneration which may help to understand the main factors leading to autism
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text small molecule transport
    PATHWAY
    metabolism
    signaling neurotransmission
    glutamate signaling pathway
    a component
  • playing a role in neuronal apoptotic death
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • GRID2IP is a GRID2-interacting protein, selectively expressed in Purkinje cell-parallel fiber synapses, and specifically interacting with the GRID2 C-terminus via its PDZ domain
  • BCL2L2 and GRID2 might interact genetically to regulate mitochondria, autophagy, and neuronal function
  • glial D-Serine regulates synaptic plasticity and cerebellar functions by interacting with GLUD2
  • TNF regulates GRID2 gene expression by activating CDC42 and GOPC genes
    • cell & other
    REGULATION
    Other role of TNF in regulation of GRID2 gene expression and its signalling pathway
    ASSOCIATED DISORDERS
    corresponding disease(s) SCAR18
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    disrupts the time course of GRM1-dependent synaptic transmission at parallel fiber-Purkinje cells synapses
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • homozygous and heterozygous "lurcher" mice (Zuo, 97)
  • GluRdelta2-/- mice display ataxia and impaired motor learning