Disease relevance of Grip1

• Glutamate receptor interacting protein 1 (GRIP1) is a scaffold protein composed of seven PDZ (Postsynaptic synaptic density-95/Discs large/Zona occludens-1) domains [1].

High impact information on Grip1

• Here we identify a synaptic PDZ domain-containing protein GRIP (glutamate receptor interacting protein) that specifically interacts with the C termini of AMPA receptors [2].
• We report the cloning of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-binding protein (ABP), a postsynaptic density (PSD) protein related to glutamate receptor-interacting protein (GRIP) with two sets of three PDZ domains, which binds the GluR2/3 AMPA receptor subunits [3].
• Serine racemase: activation by glutamate neurotransmission via glutamate receptor interacting protein and mediation of neuronal migration [4].
• Like GRIP (which we now term GRIP1), ABP-L/GRIP2 contains a seventh PDZ domain at its C terminus [5].
• We have isolated, from a rat brain cDNA library, a clone corresponding to a 2779-bp cDNA encoding a novel splice form of the glutamate receptor interacting protein-1 (GRIP1) [6].

Biological context of Grip1

• This phosphorylation is accompanied by both a reduction in the affinity of GluR2 to glutamate receptor interacting protein (GRIP), a molecule known to be critical for AMPA receptor clustering, and a significant disruption of postsynaptic GluR2 clusters [7].
• We report the activation of SR by glutamate neurotransmission involving alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors via glutamate receptor interacting protein (GRIP) and the physiologic regulation of cerebellar granule cell migration by SR [4].

Anatomical context of Grip1

• A clonal cell line prepared from immortalized GRP cells, termed GRIP-1, was also shown to retain the properties of a glial-restricted tripotential precursor [8].
• ErbB1 receptor ligands attenuate the expression of synaptic scaffolding proteins, GRIP1 and SAP97, in developing neocortex [9].
• Constitutive uterine mRNA expression of switch protein for antagonist (SPA), SRC-1, GRIP1, RAC3, RIP140, and p300 mRNAs was observed in control uteri, and treatment with ER ligands did not alter coactivator mRNA levels [10].

Associations of Grip1 with chemical compounds

• NMDA receptors interact via their NR2 subunits with PSD-95/SAP90 family proteins, whereas AMPA receptors bind via their GluR2/3 subunits to glutamate receptor-interacting protein (GRIP), AMPA receptor-binding protein (ABP), and protein interacting with C kinase 1 (PICK1) [5].
• GRIP1 PDZ7 contains a closed carboxyl group-binding pocket and a narrow alphaB/betaB-groove that is not likely to bind to classical PDZ ligands [1].
• The interaction between GRIP1 PDZ7 and a Ras guanine nucleotide exchange factor, GRASP-1, regulates synaptic distribution of AMPA receptors [1].
• Differential cellular and subcellular localization of ampa receptor-binding protein and glutamate receptor-interacting protein [11].
• 2. Grip strength and biochemical measurements, i.e. serum creatine phosphokinase (CPK) activity and creatine urinary excretion rate, together with histological studies, were performed in resting animals during a period of 14 days of PYR administration in a dose producing 20-30% whole blood acetylcholinesterase inhibition [12].

Physical interactions of Grip1

• NMR titration experiments show that GRIP1 PDZ7 binds to GRASP-1 via this hydrophobic surface [1].
• The glutamate receptor-interacting protein GRIP1 is present in glutamatergic synapses and interacts with the GluR2/3/4c subunits of the AMPA receptors [13].

Other interactions of Grip1

• Decline in SAP97 and GRIP1 levels was associated with increased abundance of lower molecular weight bands, suggesting degradation of these proteins [14].
• Proteolysis of glutamate receptor-interacting protein by calpain in rat brain: implications for synaptic plasticity [15].
• Using in situ hybridization we have examined the neuroanatomical distribution of the messenger RNAs (mRNAs) for two functionally distinct splice variants of Steroid Receptor Coactivator 1 (SRC-1/NCoA-1) and of Steroid Receptor Coactivator 2 (SRC-2/NCoA-2/GRIP-1/TIF-2) [16].
• Such coactivators include three members of the 160 kDa proteins (p160s): SRC-1, TIF2/GRIP1, and p/CIP/RAC3/ACTR/AIB1/TRAM-1 [17].

Analytical, diagnostic and therapeutic context of Grip1

• Here we show by biochemical and atomic force microscopy analyses that NEEP21, a neuronal endosomal protein necessary for receptor recycling including AMPAR, is associated with the scaffolding protein GRIP1 and the AMPAR subunit GluR2 [18].
• Although GRIP1 has been shown to be present at GABAergic synapses in cultured neurons, the use of EM (electron microscopy) immunocytochemistry in the intact brain has failed to convincingly reveal the presence of GRIP1 in GABAergic synapses [13].
• Crystallization and preliminary X-ray crystallographic studies of the sixth PDZ domain of glutamate-receptor interacting protein 1 (GRIP1) from Rattus norvegicus [19].

References