PHR1 encodes an abundant, pleckstrin homology domain-containing integral membrane protein in the photoreceptor outer segments

Shunbin Xu, Rahim Ladak, Deborah A. Swanson, Anna Soltyk, Hui Sun, Lynda Ploder, Danka Vidgen, Alessandra M.V. Duncan, Elizabeth Garami, David Valle, Roderick R. McInnes

Research output: Contribution to journalArticle

Abstract

We cloned human and murine cDNAs of a gene (designated PHR1), expressed preferentially in retina and brain. In both species, PHR1 utilizes two promoters and alternative splicing to produce four PHR1 transcripts, encoding isoforms of 243, 224, 208, and 189 amino acids, each with a pleckstrin homology domain at their N terminus and a transmembrane domain at their C terminus. Transcript 1 originates from a 5'-photoreceptor-specific promoter with at least three Crx elements ((C/T)TAATCC). Transcript 2 originates from the same promoter but lacks exon 7, which encodes 35 amino acids immediately C-terminal to the pleckstrin homology domain. Transcripts 3 and 4 originate from an internal promoter in intron 2 and either include or lack exon 7, respectively. In situ hybridization shows that PHR1 is highly expressed in photoreceptors, with lower expression in retinal ganglion cells. Immunohistochemistry localizes the PHR1 protein to photoreceptor outer segments where chemical extraction studies confirm it is an integral membrane protein. Using a series of PHR1 glutathione S-transferase fusion proteins to perform in vitro binding assays, we found PHR1 binds transducin βγ subunits but not inositol phosphates. This activity and subcellular location suggests that PHR1 may function as a previously unrecognized modulator of the phototransduction pathway.

Original languageEnglish (US)
Pages (from-to)35676-35685
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number50
DOIs
StatePublished - Dec 10 1999

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Xu, S., Ladak, R., Swanson, D. A., Soltyk, A., Sun, H., Ploder, L., Vidgen, D., Duncan, A. M. V., Garami, E., Valle, D., & McInnes, R. R. (1999). PHR1 encodes an abundant, pleckstrin homology domain-containing integral membrane protein in the photoreceptor outer segments. Journal of Biological Chemistry, 274(50), 35676-35685. https://doi.org/10.1074/jbc.274.50.35676