Golgi Dysfunctions in Ciliopathies

Masson, Justine; Ghouzzi, Vincent El

doi:10.3390/cells11182773

Cited by 6 publications

(4 citation statements)

References 60 publications

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“…S2A,B), consistent with the reported Golgi localization of Rab19 in Drosophila (Sinka et al, 2008). Although the Golgi apparatus localizes around the centrosome in many mammalian cell types (Masson and El Ghouzzi, 2022), we noted that in polarized MDCK monolayers the Golgi was not detected at the actin-clearing site around the apically docked basal body, but rather closer to the nucleus (Fig. S2B), so the basal-body localization of Rab19 appeared to be separate from its Golgi localization.…”

Section: Resultsmentioning

confidence: 89%

HOPS-dependent lysosomal fusion controls Rab19 availability for ciliogenesis in polarized epithelial cells

Hoffman

Prekeris

2023

Preprint

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Primary cilia are sensory cellular organelles crucial for organ development and homeostasis. Ciliogenesis in polarized epithelial cells requires Rab19-mediated clearing of apical cortical actin to allow the cilium to grow from the apically-docked basal body into the extracellular space. Loss of the lysosomal membrane-tethering HOPS complex disrupts this actin-clearing and ciliogenesis, but it remains unclear how ciliary function of HOPS relates to its canonical function in regulating late endosome-lysosome fusion. Here, we show that disruption of HOPS-dependent lysosomal fusion indirectly impairs actin-clearing and ciliogenesis by disrupting the targeting of Rab19 to the basal body. We also find that Rab19 functions in endolysosomal cargo trafficking apart from its previously-identified role in ciliogenesis. In summary, we show that inhibition of lysosomal fusion abnormally accumulates Rab19 on late endosomes, thus depleting Rab19 from the basal body and thereby disrupting Rab19-mediated actin-clearing and ciliogenesis.

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Section: Resultsmentioning

confidence: 89%

HOPS-dependent lysosomal fusion controls Rab19 availability for ciliogenesis in polarized epithelial cells

Hoffman

Prekeris

2023

Preprint

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“…S4A,B ), consistent with the reported Golgi localization of Rab19 in Drosophila ( Sinka et al, 2008 ). Although the Golgi localizes around the centrosome in many mammalian cell types ( Masson and El Ghouzzi, 2022 ), in polarized MDCK cell monolayers, the Golgi was not detected at the actin-clearing site around the apically docked basal body, but rather closer to the nucleus ( Fig. S4B ), so the basal body localization of Rab19 appeared to be separate from its Golgi localization.…”

Section: Resultsmentioning

confidence: 97%

HOPS-dependent lysosomal fusion controls Rab19 availability for ciliogenesis in polarized epithelial cells

Hoffman,

Prekeris

2023

Journal of Cell Science

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Primary cilia are sensory cellular organelles crucial for organ development and homeostasis. Ciliogenesis in polarized epithelial cells requires Rab19-mediated clearing of apical cortical actin to allow the cilium to grow from the apically docked basal body into the extracellular space. Loss of the lysosomal membrane-tethering homotypic fusion and protein sorting (HOPS) complex disrupts this actin clearing and ciliogenesis, but it remains unclear how the ciliary function of HOPS relates to its canonical function in regulating late endosome–lysosome fusion. Here, we show that disruption of HOPS-dependent lysosomal fusion indirectly impairs actin clearing and ciliogenesis by disrupting the targeting of Rab19 to the basal body, and that this effect is specific to polarized epithelial cells. We also find that Rab19 functions in endolysosomal cargo trafficking in addition to having its previously identified role in ciliogenesis. In summary, we show that inhibition of lysosomal fusion leads to the abnormal accumulation of Rab19 on late endosomes, thus depleting Rab19 from the basal body and thereby disrupting Rab19-mediated actin clearing and ciliogenesis in polarized epithelial cells.

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“…The loss of function of many Golgi- or cilium-resident proteins impacts both organelles and the ECM simultaneously. Moreover, there is considerable overlap between the disease pathology of some ciliopathies and Golgiopathies, particularly with respect to skeletal dysplasia ( Reiter and Leroux, 2017 ; Hellicar et al, 2022 ; Masson and El Ghouzzi, 2022 ). In the spirit of integrated studies, this review aims to examine the reciprocal relationships between the ECM, Golgi and cilium, using the golgins as an example of where these intersect.…”

Section: The Premisementioning

confidence: 99%

The factory, the antenna and the scaffold: the three-way interplay between the Golgi, cilium and extracellular matrix underlying tissue function

Stevenson

2023

Biology Open

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The growth and development of healthy tissues is dependent on the construction of a highly specialised extracellular matrix (ECM) to provide support for cell growth and migration and to determine the biomechanical properties of the tissue. These scaffolds are composed of extensively glycosylated proteins which are secreted and assembled into well-ordered structures that can hydrate, mineralise, and store growth factors as required. The proteolytic processing and glycosylation of ECM components is vital to their function. These modifications are under the control of the Golgi apparatus, an intracellular factory hosting spatially organised, protein-modifying enzymes. Regulation also requires a cellular antenna, the cilium, which integrates extracellular growth signals and mechanical cues to inform ECM production. Consequently, mutations in either Golgi or ciliary genes frequently lead to connective tissue disorders. The individual importance of each of these organelles to ECM function is well-studied. However, emerging evidence points towards a more tightly linked system of interdependence between the Golgi, cilium and ECM. This review examines how the interplay between all three compartments underpins healthy tissue. As an example, it will look at several members of the golgin family of Golgi-resident proteins whose loss is detrimental to connective tissue function. This perspective will be important for many future studies looking to dissect the cause and effect of mutations impacting tissue integrity.

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Golgi Dysfunctions in Ciliopathies

Cited by 6 publications

References 60 publications

HOPS-dependent lysosomal fusion controls Rab19 availability for ciliogenesis in polarized epithelial cells

HOPS-dependent lysosomal fusion controls Rab19 availability for ciliogenesis in polarized epithelial cells

HOPS-dependent lysosomal fusion controls Rab19 availability for ciliogenesis in polarized epithelial cells

The factory, the antenna and the scaffold: the three-way interplay between the Golgi, cilium and extracellular matrix underlying tissue function

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