Renal Cystic Proteins in the Olfactory Epithelium (OE)

In this study, we show that several proteins associated with renal cystic diseases – polycystin 1 (PC1), polycystin 2 (PC2), and Meckel‐Gruber syndrome 1 and 3 (MKS1, MKS3) – are found in the murine OE by RT‐PCR. Immunolocalization of PC1 and MKS3 in the OE revealed that PC1 is found in both dendritic knobs (from which cilia arise) and in cilia of mature olfactory neurons. Similarly, MKS3 localizes specifically to dendritic knob membranes. Rats with a disease‐causing mutation in MKS3 have reduced expression of key ciliary signaling proteins (olfactory adenylate cyclase, AC3, and the olfactory G protein). MKS1 mutant mice showed a similar reduction in AC3 expression. MKS3 mutant rats also demonstrated a decrease in acetylated α‐tubulin staining, indicating improper cilia formation and/or maintenance. This was confirmed by electron microscopy showing (a) a reduction in the number of OE cilia in mutant animals, and (b) malformation of the cilia which are present in the mutant animals (the majority of MKS3 mutant cilia had an improper number of doublets). In vitro data demonstrate that MKS3 co‐immunoprecipitates with individual olfactory receptors (ORs; 5 of the 5 ORs tested interact), implying that MKS3 may regulate OR expression/trafficking. These data show that multiple renal cystic proteins localize to the OE, where they may regulate specific aspects of the formation or physiological activities of cilia.