Human Molecular Genetics Advance Access originally published online on September 28, 2005
Human Molecular Genetics 2005 14(21):3249-3262; doi:10.1093/hmg/ddi356
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A splice form of polycystin-2, lacking exon 7, does not interact with polycystin-1
1Institut für Humangenetik, Universitätsklinikum Münster, Münster, Germany, 2Institut für Medizinische Biochemie, ZMBE, Westfälische Wilhelms-Universität Münster, Münster, Germany and 3Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Received July 27, 2005; Accepted September 21, 2005
Polycystin-2 (or polycystic kidney disease gene 2 product, PKD2) and its homologues are calcium-regulated ion channels. Mutations in PKD2 are causative for autosomal dominant polycystic kidney disease. Alternative splicing has been documented for the ‘PKD2-like’ genes as a naturally occurring event and for PKD2 in pathologic context. Here we studied naturally occurring PKD2/Pkd2 (human/murine) splice forms on the mRNA and protein levels. Systematic scanning of PKD2/Pkd2 cDNAs obtained through RT–PCR from murine tissues and human cell lines revealed alternative splice forms that were sequenced and checked for translation. We identified three major alternative transcripts of PKD2/Pkd2, PKD2/Pkd2
6, PKD2/Pkd27 and PKD2/Pkd29, and one minor splice form, PKD2/Pkd212–13, numbered according to deleted exons or parts thereof. A transcript lacking exon 7 (PKD2/Pkd27) generated significantly altered protein variant. This polycystin-27 protein appeared stable, when expressed in cell culture and apparently did not interact with polycyctin-1, which should be due to the reversed topology (extracellular) of the interacting C-terminus (intracellular in polycystin-2). Pkd27 transcript was predominantly expressed in brain and amounted to 3–6.4% of Pkd2 transcripts in the relevant organ. Moreover, both Pkd2 and Pkd27 were developmentally regulated. Polycystin-27 adds on to the number of identified polycystin molecules. The predominant expression in brain indicates a function in this organ. The inability to interact with polycystin-1 expands further the PKD1-independent functions of polycystin-2 forms.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.