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Glutamate receptor-interacting protein (GRIP) refers to either a family of proteins that bind to the glutamate receptor or specifically to the GRIP1 protein within this family. Proteins in the glutamate receptor-interacting protein (GRIP) family have been shown to interact with GluR2, a common subunit in the AMPA receptor.[1] This subunit also interacts with other proteins such as protein interacting with C-kinase1 (PICK1) and N-ethylmaleimide-sensitive fusion protein (NSF). Studies have begun to elucidate its function; however, much is still to be learned about these proteins.
Role of GRIP in AMPA cycling[edit]
AMPA receptors are constantly being transported between the cell membrane and intracellular space and it was originally thought that GRIP may be responsible for the clustering of AMPA receptors at the excitatory synapse.[1] Although it is still unclear the exact role of GRIP in this trafficking, It appears that PICK1 is more directly responsible for the clustering of AMPA receptors at the surface and that GRIP is involved in the stabilization of AMPA receptors intracellularly.[2] One study showed that when the interaction between GluR2 and GRIP is disrupted, there are no changes in the surface expression of AMPA receptors or the constitutive internalization of AMPA receptors.[3] There is, however, a reduced amount of receptors that remain internalized when receptor cycling is modified by application of AMPA-1. The ratio returns to normal when constitutive recycling is allowed to happen, suggesting that the stabilization of intracellular receptors is critical only under AMPA-induced internalization.[3]
In later studies, two proteins, GRIP-1 (often reduced to GRIP) and ABP-L (also named GRIP-2), were found to be expressed by two separate genes and their respective contributions to AMPA receptor cycling have since been well studied. Each of these proteins have different isoforms due to differential RNA splicing[4],[5]. The isoforms of GRIP-1 are named GRIP-1a and GRIP-1b while those of ABP-L are distinguished as ABP-L and pABP-L. The apparent difference in both cases is that one isoform (GRIP1b and pABP-L respectively) is capable of being conjugated with Palmitic acid, an action called Palmitoylation.
Whereas GRIP initially was thought to be involved in the stabilization of AMPA receptors either at the cell surface or intracellularly when internalization was triggered by AMPA stimulation, it now appears that the GRIP-1 isoforms are involved differentially with the stabilization of AMPA receptors after being internalized due to NMDA stimulation[6]. GRIP-1a has been shown to reduce the expected intracellular levels of AMPA receptors after NMDA stimulation. Conversely, GRIP-1b increases intracellular levels of AMPA receptors under the same conditions.
ABP-L, like GRIP-1b, associates with intracellular stores of AMPA receptors. pABP-L, however, associates with AMPA receptors as the surface membrane[7]. It has not yet been shown under what conditions these interactions are significant in the cycling of AMPA.
References[edit]
- ^ a b Dong, H; O'Brien, R; Fung, E; Lanahan, A; Worley, P; Hunganir, R (March 1997). "GRIP: A synaptic PDZ domain-containing protein that interacts with AMPA receptors". Nature. 386 (6622): 279–84.
- ^ Xia, J; Zhang, X; Staudinger, J; Huganir, R (January 1999). "Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1". Neuron. 22 (1): 179–87.
- ^ a b Braithwaite, S; Xia, H; Malenka, R (2002). "Differential roles for NSF and GRIP/ABP in AMPA receptor cycling". Proceedings of the National Academy of Sciences. 99 (10): 7096–101.
- ^ Dong, H; Zhang, P; Song, I; Petralia, R; Liao, D; Hunganir, R (15 August 1999). "Characterization of the glutamate receptor-interacting proteins GRIP1 and GRIP2". Journal of Neuroscience. 19 (16): 6930–41.
- ^ Wyszynski, M; Valtschanoff, J; Naisbitt, S; Dunah, A; Kim, E; Standaert, D; et al. (1 August 1999). "Association of AMPA receptors with a subset of glutamate receptor-interacting protein in vivo". Journal of Neuroscience. 19 (15): 6528–37.
{{cite journal}}: Explicit use of et al. in:|last7=(help) - ^ Hanley, L; Henley, J (2010). "Differential roles of GRIP1a and GRIP1b in AMPA receptor trafficking". Neuroscience Letters. 485 (3): 167–72.
- ^ DeSouza, S; Fu, J; States, B; Ziff, E (2002). "Differential palmitoylation directs the AMPA receptor-binding protein ABP to spines or to intracellular clusters". Journal of Neuroscience. 22 (9): 3493–503.