| First Author | Hackmann K | Year | 2005 |
| Journal | Hum Mol Genet | Volume | 14 |
| Issue | 21 | Pages | 3249-62 |
| PubMed ID | 16192288 | Mgi Jnum | J:104127 |
| Mgi Id | MGI:3611165 | Doi | 10.1093/hmg/ddi356 |
| Citation | Hackmann K, et al. (2005) A splice form of polycystin-2, lacking exon 7, does not interact with polycystin-1. Hum Mol Genet 14(21):3249-62 |
| abstractText | 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/Pkd2Delta6, PKD2/Pkd2Delta7 and PKD2/Pkd2Delta9, and one minor splice form, PKD2/Pkd2Delta12-13, numbered according to deleted exons or parts thereof. A transcript lacking exon 7 (PKD2/Pkd2Delta7) generated significantly altered protein variant. This polycystin-2Delta7 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). Pkd2Delta7 transcript was predominantly expressed in brain and amounted to 3-6.4% of Pkd2 transcripts in the relevant organ. Moreover, both Pkd2 and Pkd2Delta7 were developmentally regulated. Polycystin-2Delta7 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. |
