Disease relevance of Pkd2

• Targeted disruption of Pkd2 results in male sterility without affecting spermatogenesis [1].
• A common inherited cause of renal failure, autosomal dominant polycystic kidney disease results from mutations in either of two genes, PKD1 and PKD2, which encode polycystin-1 and polycystin-2, respectively [2].
• Since Ca(2+) homeostasis is a conserved mechanism for optimal muscle performance, our results raise the possibility that inactivation of just one PKD2 copy is sufficient to compromise vascular SMC contractility and function in PKD2 heterozygous patients, thus explaining their increased susceptibility to hypertension and vascular aneurysms [3].

High impact information on Pkd2

• The effect of Pkd2 mutations alone on the skeletal muscle was minimal but was exacerbated by ryanodine-induced perturbation of intracellular Ca(2+) stores [3].
• Drosophila Pkd2 is haploid-insufficient for mediating optimal smooth muscle contractility [3].
• These results suggest that PKD2 cooperates with the ryanodine receptor to promote optimal muscle contractility through intracellular Ca(2+) homeostasis [3].
• The finding that Amo functions in sperm flagella supports a common and evolutionarily conserved role for polycystin-2 proteins in both motile and nonmotile axonemal-containing structures [2].
• In agreement with this structural information, expression of PC2 in Xenopus oocytes or reconstitution of human PC2 in planar lipid bilayers produced Ca(2+)-activated cation channels [4].

Anatomical context of Pkd2

• In this report we identified a polycystin-2 homolog in Drosophila melanogaster; this homolog localized to the distal tip of the sperm flagella [2].

References