Recent advances in the molecular pathology, cell biology and genetics of ciliopathies

Abstract

Primary cilia have a broad tissue distribution and are present on most cell types in the human body. Until recently, they were considered to be redundant organelles, but progress over the past 5 years has led to an understanding of their role in normal mammalian development. The class of inherited disorders that involve aberrant ciliary function are known as ciliopathies, and although their range of severity can vary, they share some common and unexpected clinical phenotypes. The aim of this review is to assess recent insights into the structure, function and formation of primary cilia, and relate this to the pathology, molecular genetics and cell biology of the ciliopathies.

Pathological changes in primary cilia: A novel mechanism of graft cholangiopathy caused by prolonged cold preservation in a rat model of orthotopic liver transplantation

“…Liver disease caused by defects in ciliary structures and ciliary dysfunction is known as cholangiociliopathy. Cholangiociliopathy includes cystic and/or fibrotic liver diseases such as autosomal dominant polycystic kidney disease (ADPKD, caused by mutations in either PKD1 or PKD2, genes that encode PC-1 and PC-2, respectively), autosomal recessive PKD (ARPKD, caused by mutations in a single gene, PKHD1, that encodes fibrocystin), nephronophthisis (NPHP, caused by mutations in the six NPHP1-6 genes that encode nephrocystins 1-6), Bardet-Biedl syndrome (BBS, caused by mutations in the 12 BBS genes that encode BBS1-12), and Meckel-Gruber syndrome (MKS, caused by mutations in three MKS1-3 genes that encode MKS1 and meckelin) (22,23). In addition, some forms of cholecystopathy such as primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) may also be forms of cholangiociliopathy.…”

Phosphorylation‐dependent Akt–Inversin interaction at the basal body of primary cilia

“…Based on their MT components, cilia are classified as motile (9 + 2) or primary (9 + 0) (Marshall, 2008; Gerdes et al , 2009). The physiological importance of primary cilia is well established given that disruption or malfunction of cilia results in a variety of human diseases called “ciliopathy”, which includes cystic kidney diseases, hydrocephalus, blindness, obesity, polydactyly, diabetes, cognitive impairment, and developmental disorders (Otto et al , 2003; Zariwala et al , 2007; Adams et al , 2008; Marshall, 2008; Gerdes et al , 2009; Nigg & Raff, 2009; Tory et al , 2009; Hildebrandt et al , 2011). …”

“…Mutations in the INVS gene result in nephronophthisis type II (NPHP2), an autosomal recessive cystic kidney disease that progresses to end‐stage renal failure during early infancy and is occasionally associated with situs inversus (Otto et al , 2003; Saunier et al , 2005; Badano et al , 2006; Gerdes et al , 2009; Tory et al , 2009). Cystic kidney diseases are caused by an amazingly broad array of genetic mutations and manipulations (Otto et al , 2003; Zariwala et al , 2007; Adams et al , 2008; Marshall, 2008; Gerdes et al , 2009; Nigg & Raff, 2009; Tory et al , 2009; Hildebrandt et al , 2011). However, dysfunction of cilia is suggested to play a role in cystic formation (Oh & Katsanis, 2012).…”

Chronic inflammation in the respiratory tract and ciliary dyskinesia

“…Therefore, under normal conditions they are encountered in mature ciliated cells rather rarely. However, as mentioned previously, the prolonged stress may result in impaired ciliogenesis and formation of abnormal cilia, including compound and/or swollen cilia [16,17].…”

“…Interestingly, besides previously mentioned motile cilia, majority of cells in human body contain on their apical surface the single immotile cilium, known as primary cilium [13,14,16]. Primary cilia are considered as cellular sensors for physical and biochemical extracellular signals.…”