Assembly of primary cilia

Pedersen, Lotte B.; Veland, Iben R.; Schrøder, Jacob M.; Christensen, Søren T.

doi:10.1002/dvdy.21521

Cited by 188 publications

(149 citation statements)

References 153 publications

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“…28 Therefore, to provide a standard measurement scheme, cilia lengths were designated as the distance from the mother centriole to the distal tip of the visible axoneme (Fig. 2).…”

Section: Live Cell Imagingmentioning

confidence: 99%

Effect of in vitro stress‐deprivation and cyclic loading on the length of tendon cell cilia in situ

Gardner

Arnoczky

Lavagnino

2010

Journal Orthopaedic Research

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To determine the effect of loading conditions on the length of primary cilia in tendon cells in situ, freshly harvested rat tail tendons were stress-deprived (SD) for up to 72 h, cyclically loaded at 3% strain at 0.17 Hz for 24 h, or SD for 24 h followed by cyclic loading (CL) for 24 h. Tendon sections were stained for tubulin, and cilia measured microscopically. In fresh control tendons, cilia length ranged from 0.6 to 2.0 mm with a mean length of 1.1 mm. Following SD, cilia demonstrated an increase ( p < 0.001) in overall length at 24 h when compared to controls. Cilia length did not increase with time of SD ( p ¼ 0.329). Cilia in cyclically loaded tendons were shorter ( p < 0.001) compared to all SD time periods, but were not different from 0 time controls ( p ¼ 0.472). CL for 24 h decreased cilia length in 24 h SD tendons ( p < 0.001) to levels similar to those of fresh controls ( p ¼ 0.274). The results of this study demonstrate that SD resulted in an immediate and significant increase in the length of primary cilia of tendon cells, which can be reversed by cyclic tensile loading. This suggests that, as in other tissues, cilia length in tendon cells is affected by mechanical signaling from the extracellular matrix. Keywords: tendon cell; primary cilia; stress-deprivation; tensile loading Mechanical loading is essential for maintaining the health and homeostasis of tendons, although the fundamental mechanotransduction pathways by which cells mediate this process are unclear. 1 Primary cilia are sensory organelles for the detection and transmission of mechanical and chemical information from the extracellular environment of cells [2][3][4] and are known to function as mechanosensors in several connective tissue cell types, including tenocytes, osteocytes, and chondrocytes. [5][6][7][8][9][10][11] The expression of transmembrane extracellular matrix receptors (integrins) on the cilium strongly suggests that the cilium has the molecular machinery necessary to act as a mechanosensory linkage between the ECM and cytoplasmic organelles. 10 Bending or stretching of the cilium can tug on such integrins, thus generating a cascade of events ranging from internal calcium release 12 to the activation of genes 10 and signaling molecules. [13][14][15] However, the degree of cilia bending required to elicit a specific cellular response is unknown. 16 The primary cilium has been modeled as a cantilevered beam whose deflection, secondary to cell deformation or fluid flow, produces a mechanosensory signal to the cell. 17 As such, is it logical to assume that the longer the beam (cilium), the more sensitive it will be to smaller deflection forces and, conversely, the shorter the beam, the less sensitive it will be. 17 Indeed, previous studies have suggested that the level of mechanical stimuli experienced by a cell could lead to remodeling of its ciliary structure through changes in its length. 16 Such modifications could, theoretically, make the cilia more or less sensitive to mechanical signals transmitted by the e...

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“…28 Therefore, to provide a standard measurement scheme, cilia lengths were designated as the distance from the mother centriole to the distal tip of the visible axoneme (Fig. 2).…”

Section: Live Cell Imagingmentioning

confidence: 99%

Effect of in vitro stress‐deprivation and cyclic loading on the length of tendon cell cilia in situ

Gardner

Arnoczky

Lavagnino

2010

Journal Orthopaedic Research

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“…Meanwhile, Golgi-derived vesicles form a sheath surrounding the centriole/basal body. After reaching the cell surface, the sheath fuses with the plasma membrane and forms the ciliary membrane [8,9]. Vesicular trafficking events are expected to be important for ciliogenesis because ciliary proteins must be transported from the Golgi to the basal body and the elongating ciliary axoneme.…”

Section: Introductionmentioning

confidence: 99%

“…Vesicular trafficking events are expected to be important for ciliogenesis because ciliary proteins must be transported from the Golgi to the basal body and the elongating ciliary axoneme. Genetic and biochemical studies carried out in C. rein- hardtii and C. elegans have provided many insights into the mechanism of the assembly of the ciliary axoneme via the intraflagellar transport (IFT)-mediated trafficking [9,10]. Recent studies indicate that other vesicular trafficking events are involved in ciliogenesis as well.…”

Section: Introductionmentioning

confidence: 99%

A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo

Chen

et al. 2011

Cell Res

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Sorting nexins (SNXs) are phosphoinositide-binding proteins implicated in the sorting of various membrane proteins in vitro, but the in vivo functions of them remain largely unknown. We reported previously that SNX10 is a unique member of the SNX family genes in that it has vacuolation activity in cells. We investigate the biological function of SNX10 by loss-of-function assay in this study and demonstrate that SNX10 is required for the formation of primary cilia in cultured cells. In zebrafish, SNX10 is involved in ciliogenesis in the Kupffer's vesicle and essential for left-right patterning of visceral organs. Mechanistically, SNX10 interacts with V-ATPase complex and targets it to the centrosome where ciliogenesis is initiated. Like SNX10, V-ATPase regulates ciliogenesis in vitro and in vivo and does so synergistically with SNX10. We further discover that SNX10 and V-ATPase regulate the ciliary trafficking of Rab8a, which is a critical regulator of ciliary membrane extension. These results identify an SNX10/V-ATPaseregulated vesicular trafficking pathway that is crucial for ciliogenesis, and reveal that SNX10/V-ATPase, through the regulation of cilia formation in various organs, play an essential role during early embryonic development.

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“…Construction of the ciliary axoneme requires intraflagellar transport (IFT), a bidirectional transport system driven by motor protein complexes that bring axonemal precursors to the growing tip of the cilium and return turnover products to the base [66]. Since IFT20 and IFT88 are required for effective ciliogenesis [67][68][69], we assessed the sub-cellular localization and expression of these proteins in the wt and OSE cell cultures grown in the presence or absence of serum.…”

Section: Characterization and Isolation Of Human Ose Cells In Culturesmentioning

confidence: 99%

“…progression [35,66]. Therefore, we speculated whether the low frequency of primary cilia in cancer OSE cells results from a high rate of proliferation.…”

Section: Characterization and Isolation Of Human Ose Cells In Culturesmentioning

confidence: 99%

Epithelial Ovarian Cancer

Berek¹,

Bast²

Encyclopedia of Diagnostic Imaging

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Background: Ovarian cancer is the fourth leading cause of cancer-related deaths among women in Denmark, largely due to the advanced stage at diagnosis in most patients. Approximately 90% of ovarian cancers originate from the single-layered ovarian surface epithelium (OSE). Defects in the primary cilium, a solitary sensory organelle in most cells types including OSE, were recently implicated in tumorigenesis, mainly due to deregulation of ciliary signaling pathways such as Hedgehog (Hh) signaling. However, a possible link between primary cilia and epithelial ovarian cancer has not previously been investigated. Methods: The presence of primary cilia was analyzed in sections of fixed human ovarian tissue as well as in cultures of normal human ovarian surface epithelium (OSE) cells and two human OSE-derived cancer cell lines. We also used immunofluorescence microscopy, western blotting, RT-PCR and siRNA to investigate ciliary signaling pathways in these cells.

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Assembly of primary cilia

Cited by 188 publications

References 153 publications

Effect of in vitro stress‐deprivation and cyclic loading on the length of tendon cell cilia in situ

Effect of in vitro stress‐deprivation and cyclic loading on the length of tendon cell cilia in situ

A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo

Epithelial Ovarian Cancer

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