A direct functional link between the multi-PDZ domain protein GRIP1 and the Fraser syndrome protein Fras1

Kogo Takamiya, Vassiliki Kostourou, Susanne Adams, Shalini Jadeja, Georges Chalepakis, Peter J. Scambler, Richard L Huganir, Ralf H. Adams

Research output: Contribution to journalArticle

Abstract

Cell adhesion to extracellular matrix (ECM) proteins is crucial for the structural integrity of tissues and epithelial-mesenchymal interactions mediating organ morphogenesis. Here we describe how the loss of a cytoplasmic multi-PDZ scaffolding protein, glutamate receptor interacting protein 1 (GRIP1), leads to the formation of subepidermal hemorrhagic blisters, renal agenesis, syndactyly or polydactyly and permanent fusion of eyelids (cryptophthalmos). Similar malformations are characteristic of individuals with Fraser syndrome and animal models of this human genetic disorder, such as mice carrying the blebbed mutation (bl) in the gene encoding the Fras1 ECM protein. GRIP1 can physically interact with Fras1 and is required for the localization of Fras1 to the basal side of cells. In one animal model of Fraser syndrome, the eye-blebs (eb) mouse, Grip1 is disrupted by a deletion of two coding exons. 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.

Original languageEnglish (US)
Pages (from-to)172-177
Number of pages6
JournalNature Genetics
Volume36
Issue number2
DOIs
StatePublished - Feb 2004

Fingerprint

Fraser Syndrome
Receptor-Interacting Protein Serine-Threonine Kinases
PDZ Domains
Glutamate Receptors
Extracellular Matrix Proteins
Blister
Animal Models
Syndactyly
Polydactyly
Inborn Genetic Diseases
Proteins
Medical Genetics
Eyelids
Morphogenesis
Cell Adhesion
Cell Communication
Embryonic Development
Exons
Epithelium
Mutation

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Takamiya, K., Kostourou, V., Adams, S., Jadeja, S., Chalepakis, G., Scambler, P. J., ... Adams, R. H. (2004). A direct functional link between the multi-PDZ domain protein GRIP1 and the Fraser syndrome protein Fras1. Nature Genetics, 36(2), 172-177. https://doi.org/10.1038/ng1292

A direct functional link between the multi-PDZ domain protein GRIP1 and the Fraser syndrome protein Fras1. / Takamiya, Kogo; Kostourou, Vassiliki; Adams, Susanne; Jadeja, Shalini; Chalepakis, Georges; Scambler, Peter J.; Huganir, Richard L; Adams, Ralf H.

In: Nature Genetics, Vol. 36, No. 2, 02.2004, p. 172-177.

Research output: Contribution to journalArticle

Takamiya, K, Kostourou, V, Adams, S, Jadeja, S, Chalepakis, G, Scambler, PJ, Huganir, RL & Adams, RH 2004, 'A direct functional link between the multi-PDZ domain protein GRIP1 and the Fraser syndrome protein Fras1', Nature Genetics, vol. 36, no. 2, pp. 172-177. https://doi.org/10.1038/ng1292
Takamiya K, Kostourou V, Adams S, Jadeja S, Chalepakis G, Scambler PJ et al. A direct functional link between the multi-PDZ domain protein GRIP1 and the Fraser syndrome protein Fras1. Nature Genetics. 2004 Feb;36(2):172-177. https://doi.org/10.1038/ng1292
Takamiya, Kogo ; Kostourou, Vassiliki ; Adams, Susanne ; Jadeja, Shalini ; Chalepakis, Georges ; Scambler, Peter J. ; Huganir, Richard L ; Adams, Ralf H. / A direct functional link between the multi-PDZ domain protein GRIP1 and the Fraser syndrome protein Fras1. In: Nature Genetics. 2004 ; Vol. 36, No. 2. pp. 172-177.
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