Two distantly positioned PDZ domains mediate multivalent INAD-phospholipase C interactions essential for G protein-coupled signaling
| Autor: | Karen Miller, Ronald W. Raab, De Mao Chen, William S. Stark, Min Li, Zhi Chun Lai, Randall D. Shortridge, Ying Li, Rika van Huizen |
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| Rok vydání: | 1998 |
| Předmět: |
G protein
Recombinant Fusion Proteins PDZ domain Molecular Sequence Data Phospholipase C beta General Biochemistry Genetics and Molecular Biology Animals Genetically Modified GTP-binding protein regulators GTP-Binding Proteins Animals Drosophila Proteins Amino Acid Sequence Binding site Eye Proteins Molecular Biology Vision Ocular Genetics Binding Sites General Immunology and Microbiology Phospholipase C biology Sequence Homology Amino Acid Effector General Neuroscience biology.organism_classification Cell biology Isoenzymes Drosophila melanogaster Mutagenesis Type C Phospholipases Photoreceptor Cells Invertebrate Visual phototransduction Research Article |
| Zdroj: | The EMBO journal. 17(8) |
| ISSN: | 0261-4189 |
| Popis: | Drosophila INAD, which contains five tandem protein interaction PDZ domains, plays an important role in the G protein-coupled visual signal transduction. Mutations in InaD alleles display mislocalization of signaling molecules of phototransduction which include the essential effector, phospholipase C-beta (PLC-beta), which is also known as NORPA. The molecular and biochemical details of this functional link are unknown. We report that INAD directly binds to NORPA via two terminally positioned PDZ1 and PDZ5 domains. PDZ1 binds to the C-terminus of NORPA, while PDZ5 binds to an internal region overlapping with the G box-homology region (a putative G protein-interacting site). The NORPA proteins lacking binding sites, which display normal basal PLC activity, can no longer associate with INAD in vivo. These truncations cause significant reduction of NORPA protein expression in rhabdomeres and severe defects in phototransduction. Thus, the two terminal PDZ domains of INAD, through intermolecular and/or intramolecular interactions, are brought into proximity in vivo. Such domain organization allows for the multivalent INAD-NORPA interactions which are essential for G protein-coupled phototransduction. |
| Databáze: | OpenAIRE |
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