A splice form of polycystin-2, lacking exon 7, does not interact with polycystin-1.
نویسندگان
چکیده
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.
منابع مشابه
Polycystin-1 distribution is modulated by polycystin-2 expression in mammalian cells.
Mutations in PKD1 and PKD2, the genes that encode polycystin-1 and polycystin-2 respectively, account for almost all cases of autosomal dominant polycystic kidney disease. Although the polycystins are believed to interact in vivo, the two proteins often display dissimilar patterns and gradients of expression during development. In an effort to understand this apparent discrepancy, we investigat...
متن کاملAutosomal dominant polycystic kidney disease: clues to pathogenesis.
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutation of one of two genes: PKD1 (16p13.3) or PKD2 (4q13-23). PKD1 accounts for approximately 85% of pedigrees and is associated with significantly more severe cystic disease. The ADPKD genes encode proteins, polycystin-1 and polycystin-2, which are very different in size and structure, but which have a region of homology and m...
متن کاملPolycystin-1L2 is a novel G-protein-binding protein.
Mutations in genes encoding polycystin-1 (PC1) and polycystin-2 cause autosomal dominant polycystic kidney disease. The polycystin protein family is composed of Ca2+-permeable pore-forming subunits and receptor-like integral membrane proteins. Here we describe a novel member of the polycystin-1-like subfamily, polycystin-1L2 (PC1L2), encoded by PKD1L2, which has various alternative splicing for...
متن کاملHyperphosphorylation of polycystin-2 at a critical residue in disease reveals an essential role for polycystin-1-regulated dephosphorylation.
Mutations in PKD1 (85%) or PKD2 (15%) account for almost all cases of autosomal dominant polycystic kidney disease (ADPKD). The ADPKD proteins, termed as polycystin-1 (PC1) and polycystin-2 (PC2), interact via their C-termini to form a receptor-ion channel complex whose function and regulation are not fully understood. Here, we report the first phosphorylated residue (Ser(829)) in PC2, whose de...
متن کاملConstitutive activation of G-proteins by polycystin-1 is antagonized by polycystin-2.
Polycystin-1 (PC1), a 4,303-amino acid integral membrane protein of unknown function, interacts with polycystin-2 (PC2), a 968-amino acid alpha-type channel subunit. Mutations in their respective genes cause autosomal dominant polycystic kidney disease. Using a novel heterologous expression system and Ca(2+) and K(+) channels as functional biosensors, we found that full-length PC1 functioned as...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Human molecular genetics
دوره 14 21 شماره
صفحات -
تاریخ انتشار 2005