CPLANE Complex and Ciliopathies

Abstract

Primary cilia are non-motile organelles associated with the cell cycle, which can be found in most vertebrate cell types. Cilia formation occurs through a process called ciliogenesis, which involves several mechanisms including planar cell polarity (PCP) and the Hedgehog (Hh) signaling pathway. Some gene complexes, such as BBSome or CPLANE (ciliogenesis and planar polarity effector), have been linked to ciliogenesis. CPLANE complex is composed of INTU, FUZ and WDPCP, which bind to JBTS17 and RSG1 for cilia formation. Defects in these genes have been linked to a malfunction of intraflagellar transport and defects in the planar cell polarity, as well as defective activation of the Hedgehog signalling pathway. These faults lead to defective cilium formation, resulting in ciliopathies, including orofacial–digital syndrome (OFDS) and Bardet–Biedl syndrome (BBS). Considering the close relationship, between the CPLANE complex and cilium formation, it can be expected that defects in the genes that encode subunits of the CPLANE complex may be related to other ciliopathies.

CORUM: the comprehensive resource of mammalian protein complexes–2022

“…Non-motile (primary) cilia are sensory organelles, that transduce signals from the environment or from other cells, motile cilia move extracellular fluids like cerebrospinal fluid or propel sperm cells. The FCG ‘Cilium assembly’ comprises complexes like the CPLANE complex, the intraflagellar transport complexes IFT-A and IFT-B, or the BBSome ( 28 ) which interact in the generation of cilia. As cilia are found in most vertebrate cell types, there is a wide range of clinical features associated with disorders caused by alteration of cilia structure or function, the so called ciliopathies ( 28 ).…”

“…The FCG ‘Cilium assembly’ comprises complexes like the CPLANE complex, the intraflagellar transport complexes IFT-A and IFT-B, or the BBSome ( 28 ) which interact in the generation of cilia. As cilia are found in most vertebrate cell types, there is a wide range of clinical features associated with disorders caused by alteration of cilia structure or function, the so called ciliopathies ( 28 ). Mutations in the subunits of the CPLANE, IFT-A, IFT-B and BBSome complexes can cause diseases like Bardet-Biedl syndrome, Short-rib thoracic dysplasia, Retinitis pigmentosa, Nephronophthisis or Spermatogenic failure, which reflect the broad spectrum of phenotypes associated with ciliopathies.…”

Genome-wide screening reveals the genetic basis of mammalian embryonic eye development

“…In addition to the CPLANE genes, our search uncovered a number of additional ciliopathy genes associated with multi-systemic, brain, kidney, and eye ciliopathies ( Cep135 , Innp5e , Pex6 , Togaram1 , see Additional file 1 : Table S3). The members of the CPLANE complex, by contributing to the formation of primary cilia, are important regulators of the hedgehog and WNT signaling pathways [ 45 ]. Restricted spatial distribution of SHH is essential for the specification of eye progenitor cells [ 46 ], as SHH-mediated induction of embryonic tissues including eye formation is dependent on the establishment of SHH morphogenic gradients [ 45 ].…”

“…The members of the CPLANE complex, by contributing to the formation of primary cilia, are important regulators of the hedgehog and WNT signaling pathways [ 45 ]. Restricted spatial distribution of SHH is essential for the specification of eye progenitor cells [ 46 ], as SHH-mediated induction of embryonic tissues including eye formation is dependent on the establishment of SHH morphogenic gradients [ 45 ]. The association between aberrant primary cilium formation, SHH expression, and eye defects have been demonstrated for SUFU, Fuz, JBTS17/ Cplane1 , TBCD132, and TCTN3.…”

Cytoskeletal networks in primary cilia: Current knowledge and perspectives

“…Given the ubiquitous distribution and functional importance of cilia in human beings, abnormalities in ciliary structure and function can result in an ever‐expanding list of severe human disorders, collectively referred to as the ciliopathies, which include the Bardet–Biedl syndrome, the Joubert syndrome, the Meckel syndrome, polycystic kidney disease, retinal degeneration, abnormal situs, obesity, diabetes, etc. (Hildebrandt et al, 2011; Martin‐Salazar & Valverde, 2022). To date, more than 35 types of ciliopathies have been reported with over 400 ciliopathy‐associated genes being identified (Best et al, 2022; Reiter & Leroux, 2017).…”