Two distantly positioned PDZ domains mediate multivalent INAD-phospholipase C interactions essential for G protein-coupled signaling

Rika Van Huizen, Karen Miller, De Mao Chen, Ying Li, Zhi Chun Lai, Ronald W. Raab, William S. Stark, Randall D. Shortridge, Min Li

Research output: Contribution to journalArticle

Abstract

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-β (PLC-β), 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.

Original languageEnglish (US)
Pages (from-to)2285-2297
Number of pages13
JournalEMBO Journal
Volume17
Issue number8
DOIs
StatePublished - Apr 15 1998

Keywords

  • G protein
  • INAD
  • PDZ
  • PLC

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Van Huizen, R., Miller, K., Chen, D. M., Li, Y., Lai, Z. C., Raab, R. W., Stark, W. S., Shortridge, R. D., & Li, M. (1998). Two distantly positioned PDZ domains mediate multivalent INAD-phospholipase C interactions essential for G protein-coupled signaling. EMBO Journal, 17(8), 2285-2297. https://doi.org/10.1093/emboj/17.8.2285