Cilium lash

Ities to that of the Notch pathway. In response to a lack of fluid flow or tubule obstruction, the COOH-terminal region of PC-1 undergoes regulated intramembrane proteolysis RIP ; 11 ; . The COOH-terminal region of PC-1 translocates to the nucleus, where it regulates AP-1 activity Ref. 11 and reviewed in Ref. 20 ; . This finding opens the possibility that cilia are important in mechanosensory reception that results in changes in gene transcription through proteolysis of PC-1; however, because PC-1 is localized to multiple sites in the cell, it remains to be determined whether this occurs in the cilia. Intriguingly, the homologs of polycystin-1 lov-1 ; and polycystin-2 pkd-2 ; in C. elegans have also been localized to cilia of sensory neurons in males 2 ; . Whereas the cilia in lov-1 or pkd-2 mutants appear normal, the mutants exhibit abnormal male mating behavior that is thought to be due to defects in a mechano- or chemosensory role of the cilia 2, 25 ; . What is not known is whether these defects in mating behavior are associated with altered calcium signaling or PC-1 processing as proposed for fluid flow-mediated signaling in the mammalian collecting duct. In addition to the proteins involved in PKD, proteins associated with cysts in non-PKD disorders such as nephronophthisis nephrocystin-1, nephrocystin-2, and nephrocystin-4 ; and Bardet-Biedl syndrome BBS 1 8 ; have also been reported to localize to the cilia and or basal body Fig. 2 ; . Although the function of these proteins in the renal epithelium of mammals remains to be fully evaluated, in C. elegans two BBS proteins, BBS-7 and BBS-8, appear to be involved in regulating rates of IFT movement along the cilia axoneme, as defects in these genes result in abnormal ciliogenesis 7 ; . In contrast, the cilia of C. elegans nephrocystin-1 and nephrocystin-4 mutants appear morphologically normal; however, these mutants display behavioral abnormalities typical of cilia-mediated sensory defects 86a, 87 ; . These include suppressed male mating efficiency, defects in chemotaxis toward volatile attractants, and extended lifespan. Interestingly, in C. elegans the nephrocystin-1 and nephrocystin-4 proteins are not found in the cilia but rather at the transition zone analogous to the mammalian basal body ; at the base of the cilia. This further raises the possibility that both the primary renal cilium and basal body have important sensory functions that may be impaired in human nephronophthisis and cystic kidney disease patients. Additional evidence supporting the direct involvement of cilia in the development of cystic kidneys has resulted from the characterization of a large number of cystic kidney disease mouse models Table 1; see Ref. 19 for a recent review ; . Many of these models have now been shown to be associated with mutations in proteins residing in the cilium. One of the murine models that helped to uncover the connection between cilia and cystic kidney disease was the Oak Ridge Polycystic Kidney Tg737rpk ; mutant mouse. Tg737rpk is a hypomorphic allele of the Tg737 gene encoding the IFT protein Polaris 82 ; . Analysis of the Polaris homolog in Chlamydomonas and C. elegans indicated that it is a complex B protein involved in anterograde movement of the IFT raft 23, 55 ; . Due to defects in IFT, Tg737rpk mice develop cystic lesions in the kidney that resemble the pathology seen in human ARPKD patients. Analysis of their renal epithelium reveals that the primary cilia are severely stunted 55, 82 ; and, furthermore, that the mutant cells possess an abrogated calcium signal in response to fluid flow.

What is cilium husk