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Gene Review

Grip1  -  glutamate receptor interacting protein 1

Mus musculus

Synonyms: 4931400F03Rik, GRIP, GRIP-1, Glutamate receptor-interacting protein 1, eb
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Disease relevance of Grip1


High impact information on Grip1

  • Our data indicate that GRIP1 is required for normal cell-matrix interactions during early embryonic development and that inactivation of Grip1 causes Fraser syndrome-like defects in mice [1].
  • Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites [4].
  • To explore the function of GRIP1 in hippocampal neurons, we used RNA interference (RNAi) to knock down the expression of GRIP1 [5].
  • Knockdown of GRIP1 by small interfering RNA (siRNA) in cultured hippocampal neurons caused a loss of dendrites, associated with mislocalization of the GRIP-interacting proteins GIuR2 (AMPA receptor subunit), EphB2 (receptor tyrosine kinase) and KIF5 (also known as kinesin 1; microtubule motor) [5].
  • Factor recruitment and TIF2/GRIP1 corepressor activity at a collagenase-3 response element that mediates regulation by phorbol esters and hormones [6].

Biological context of Grip1

  • Localization of the mouse glucocorticoid receptor-interacting protein 1 gene (Grip1) to proximal chromosome 1 by linkage analysis [7].
  • To clarify the physiological functions of GRIP, we cloned mouse GRIP1, and found that there are three sites for alternative splicing and two putative translational start codons by characterizing GRIP1 cDNA clones and reverse transcription-polymerase chain reaction products [8].
  • GRIP1 was chosen as a transgene because it interacts with AMPA receptors and is involved in glutamate receptor signaling [9].
  • GRIP1 controls dendrite morphogenesis by regulating EphB receptor trafficking [5].
  • Our findings are consistent with the possibility that GRIP1 acts as a scaffold to promote interaction between proteins that function during meiosis [10].

Anatomical context of Grip1


Associations of Grip1 with chemical compounds

  • GRIP1tau is a novel isoform of glutamate receptor-interacting protein 1 (GRIP1) that associates with the cytoplasmic domain of the alpha-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate (AMPA)-type glutamate receptor [12].
  • These results indicate that PLCdelta4 binds via its C2 domain to the PDZ6 or PDZ7 domain of GRIP1, and that this association may play a role in spermatogenesis [13].
  • To identify the interaction proteins for the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor subunit glutamate receptor-interacting protein 1 (GRIP1), GRIP1 interactions with microtubule-associated protein (MAP)-1B light chain (LC) were investigated [14].
  • To understand the mechanism of this PB-independent nuclear accumulation, we have examined the mCAR structural determinants of its GRIP1-mediated nuclear localization [15].
  • The proteasome inhibitors MG132 and lactacystin abolished the PKA-mediated degradation of GRIP1 [16].

Physical interactions of Grip1

  • NG2 exhibits a PDZ binding motif at the extreme COOH terminus which binds to the seventh PDZ domain of GRIP1 [11].
  • GRIP1 is known to bind to the GluRB subunit of the AMPA glutamate receptor expressed by subpopulations of neurons and immature glial cells [11].
  • Furthermore, Shank2 interacted with GRIP1 in the cerebellum [17].

Other interactions of Grip1


Analytical, diagnostic and therapeutic context of Grip1

  • As would be expected if this complex is functional, both gene targeting and dominant negative experiments of heavy chains of mouse kinesin showed abnormal localization of GRIP1 [4].
  • Co-immunoprecipitation from rat brains showed that transgenic GRIP1 is in complex with the endogenous GluR2 subunit of AMPA receptors [9].
  • DESIGN: Two novel polyclonal antibodies against amino acids 34-47 and 468-481 of GRIP1 were raised and characterized in order to study the GRIP1 expression with immunohistochemistry [19].
  • GRIP1 was down-regulated in transiently transfected COS-1 cells after treatment with 8-para-chlorophenylthio-cAMP or forskolin and 3-isobutyl-1-methylxanthine and in adrenocortical Y1 cells after incubation with adrenocorticotropic hormone [16].
  • In gel shift analysis, binding to CAR was observed only with GRIP1 fragments containing the C-terminal region, and the binding was increased by a CAR agonist and decreased by a CAR antagonist [20].


  1. A direct functional link between the multi-PDZ domain protein GRIP1 and the Fraser syndrome protein Fras1. Takamiya, K., Kostourou, V., Adams, S., Jadeja, S., Chalepakis, G., Scambler, P.J., Huganir, R.L., Adams, R.H. Nat. Genet. (2004) [Pubmed]
  2. Applications for multifrequency ultrasound biomicroscopy in mice from implantation to adulthood. Zhou, Y.Q., Foster, F.S., Qu, D.W., Zhang, M., Harasiewicz, K.A., Adamson, S.L. Physiol. Genomics (2002) [Pubmed]
  3. The human glucocorticoid receptor (hGR) beta isoform suppresses the transcriptional activity of hGRalpha by interfering with formation of active coactivator complexes. Charmandari, E., Chrousos, G.P., Ichijo, T., Bhattacharyya, N., Vottero, A., Souvatzoglou, E., Kino, T. Mol. Endocrinol. (2005) [Pubmed]
  4. Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites. Setou, M., Seog, D.H., Tanaka, Y., Kanai, Y., Takei, Y., Kawagishi, M., Hirokawa, N. Nature (2002) [Pubmed]
  5. GRIP1 controls dendrite morphogenesis by regulating EphB receptor trafficking. Hoogenraad, C.C., Milstein, A.D., Ethell, I.M., Henkemeyer, M., Sheng, M. Nat. Neurosci. (2005) [Pubmed]
  6. Factor recruitment and TIF2/GRIP1 corepressor activity at a collagenase-3 response element that mediates regulation by phorbol esters and hormones. Rogatsky, I., Zarember, K.A., Yamamoto, K.R. EMBO J. (2001) [Pubmed]
  7. Localization of the mouse glucocorticoid receptor-interacting protein 1 gene (Grip1) to proximal chromosome 1 by linkage analysis. Welch, C.L., Xia, Y.R., Hong, H., Stallcup, M.R., Lusis, A.J. Mamm. Genome (1997) [Pubmed]
  8. Differential palmitoylation of two mouse glutamate receptor interacting protein 1 forms with different N-terminal sequences. Yamazaki, M., Fukaya, M., Abe, M., Ikeno, K., Kakizaki, T., Watanabe, M., Sakimura, K. Neurosci. Lett. (2001) [Pubmed]
  9. Generation of lentiviral transgenic rats expressing glutamate receptor interacting protein 1 (GRIP1) in brain, spinal cord and testis. Nakagawa, T., Feliu-Mojer, M.I., Wulf, P., Lois, C., Sheng, M., Hoogenraad, C.C. J. Neurosci. Methods (2006) [Pubmed]
  10. Interaction of DNA polymerase beta with GRIP1 during meiosis. Jonason, A.S., Baker, S.M., Sweasy, J.B. Chromosoma (2001) [Pubmed]
  11. The proteoglycan NG2 is complexed with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by the PDZ glutamate receptor interaction protein (GRIP) in glial progenitor cells. Implications for glial-neuronal signaling. Stegmüller, J., Werner, H., Nave, K.A., Trotter, J. J. Biol. Chem. (2003) [Pubmed]
  12. GRIP1tau, a novel PDZ domain-containing transcriptional activator, cooperates with the testis-specific transcription elongation factor SII-T1. Nakata, A., Ito, T., Nagata, M., Hori, S., Sekimizu, K. Genes Cells (2004) [Pubmed]
  13. Phospholipase Cdelta4 associates with glutamate receptor interacting protein 1 in testis. Irino, Y., Ichinohe, M., Nakamura, Y., Nakahara, M., Fukami, K. J. Biochem. (2005) [Pubmed]
  14. Glutamate receptor-interacting protein 1 protein binds to the microtubule-associated protein. Seog, D.H. Biosci. Biotechnol. Biochem. (2004) [Pubmed]
  15. Structural determinants of constitutive androstane receptor required for its glucocorticoid receptor interacting protein-1-mediated nuclear accumulation. Xia, J., Kemper, B. J. Biol. Chem. (2005) [Pubmed]
  16. cAMP-dependent protein kinase regulates ubiquitin-proteasome-mediated degradation and subcellular localization of the nuclear receptor coactivator GRIP1. Hoang, T., Fenne, I.S., Cook, C., Børud, B., Bakke, M., Lien, E.A., Mellgren, G. J. Biol. Chem. (2004) [Pubmed]
  17. Direct interaction of GluRdelta2 with Shank scaffold proteins in cerebellar Purkinje cells. Uemura, T., Mori, H., Mishina, M. Mol. Cell. Neurosci. (2004) [Pubmed]
  18. The extracellular matrix gene Frem1 is essential for the normal adhesion of the embryonic epidermis. Smyth, I., Du, X., Taylor, M.S., Justice, M.J., Beutler, B., Jackson, I.J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  19. Localization of glucocorticoid receptor interacting protein 1 in murine tissues using two novel polyclonal antibodies. Puustinen, R., Sarvilinna, N., Manninen, T., Tuohimaa, P., Ylikomi, T. Eur. J. Endocrinol. (2001) [Pubmed]
  20. Glucocorticoid receptor-interacting protein 1 mediates ligand-independent nuclear translocation and activation of constitutive androstane receptor in vivo. Min, G., Kemper, J.K., Kemper, B. J. Biol. Chem. (2002) [Pubmed]
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