Polycystin expression is temporally and spatially regulated during renal development

Abstract

Mutations in PKD1 cause autosomal dominant polycystic kidney disease (ADPKD), a common genetic disease in which cysts form from kidney tubules. The predicted product of this gene is a novel protein with cell-adhesive and membrane-spanning domains. To test the hypothesis that polycystin, the product of the PKD1 gene, is a cell adhesion molecule, we raised antibodies against peptides derived from the unduplicated, membrane-spanning portion of the predicted amino acid sequence. These antibodies recognized membrane-associated polypeptides of 485 and 245 kDa in human fetal kidney homogenates. Expression was greater in fetal than adult kidney by both Western blot analysis and immunofluorescence. In fetal kidney, polycystin was localized to the plasma membranes of ureteric bud and comma and S-shaped bodies. However, in more mature tubules in fetal kidney, in adult kidney, and in polycystic kidney, the majority of polycystin staining was intracellular. The temporal and spatial regulation of polycystin expression during renal development lead us to speculate that polycystin may play a role in nephrogenesis.

c-Myc Signalling in the Genetic Mechanism of Polycystic Kidney Disease

“…In ADPKD patients, expression levels of the PKD1/PKD2 mutated allele can be strongly or mildly reduced. Paradoxically, PKD1/PKD2 and PC1/PC2 are found overexpressed in human ADPKD kidneys (3,(62)(63)(64)(65)(66)(67). The severity of the ADPKD cystogenic mechanism(s) is likely to depend on modulation of the remaining non-mutant copy of PKD1/PKD2 potentially through de novo mutations, a stochastic event, altered functional role of polycystins and/or epigenetic inheritance that are actively under study.…”

Ciliary dysfunction in polycystic kidney disease: an emerging model with polarizing potential

“…Immunohistochemical detection of polycystin-1 in human renal tissue indicates polycystin-1 is expressed in most nephron segments, although the precise spatial pattern remains unclear (7,(61)(62)(63). This may be due to variations in the temporal and spatial expression pattern for polycystin-1 between species confounded by changing cellular localizations during development (63,64).…”

“…This may be due to variations in the temporal and spatial expression pattern for polycystin-1 between species confounded by changing cellular localizations during development (63,64). This is further complicated by individual studies using different antibodies to various regions of polycystin-1, introducing an uncertainty in the detection of full-length polycystin-1, and detection of protein products from homologous genes.…”

“…This is further complicated by individual studies using different antibodies to various regions of polycystin-1, introducing an uncertainty in the detection of full-length polycystin-1, and detection of protein products from homologous genes. Moreover, antigen detection in tissue is difficult, often masked from fixation and the documented results regarding the degradation of polycystin-1 (63).…”

“…Developmental studies show polycystin-1 localizes to the distal portion of the uteric bud (15) as well as the portion of the uteric bud deep within the nephrogenic zone (63). However, murine polycystin-1 localization studies have also demonstrated low levels of polycystin-1 at the uteric bud (64) along with no detectable PKD1 mRNA in the uteric bud of human embryos at 10 weeks, challenging the role of polycystin-1 in nephrogenic induction (65).…”