Crumbs organizes the transport machinery by regulating apical levels of PI(4,5)P2 in Drosophila

Lattner, Johanna; Leng, Weihua; Knust, Elisabeth; Brankatschk, Marko; Flores-Benítez, David

doi:10.7554/elife.50900

Cited by 18 publications

(26 citation statements)

References 214 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PI(4,5)P 2 is apically enriched and has been proposed as an apical identity determinant. In the polarized secretory epithelium of the salivary gland of the Drosophila larva, the protein Crumbs regulates the apical level of PI(4,5)P 2 by regulating Pten and Ocrl localization 36 . Given that PI(4,5)P 2 regulates vesicle exocytosis 30 , polarized vesicle transport controlled by PI(4,5)P 2 may play a critical role in the determination of epithelial characteristics.…”

Section: Discussionmentioning

confidence: 99%

Plasma membrane phosphatidylinositol (4,5)-bisphosphate is critical for determination of epithelial characteristics

et al. 2022

View full text Add to dashboard Cite

Epithelial cells provide cell-cell adhesion that is essential to maintain the integrity of multicellular organisms. Epithelial cell-characterizing proteins, such as epithelial junctional proteins and transcription factors are well defined. However, the role of lipids in epithelial characterization remains poorly understood. Here we show that the phospholipid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] is enriched in the plasma membrane (PM) of epithelial cells. Epithelial cells lose their characteristics upon depletion of PM PI(4,5)P2, and synthesis of PI(4,5)P2 in the PM results in the development of epithelial-like morphology in osteosarcoma cells. PM localization of PARD3 is impaired by depletion of PM PI(4,5)P2 in epithelial cells, whereas expression of the PM-targeting exocyst-docking region of PARD3 induces osteosarcoma cells to show epithelial-like morphological changes, suggesting that PI(4,5)P2 regulates epithelial characteristics by recruiting PARD3 to the PM. These results indicate that a high level of PM PI(4,5)P2 plays a crucial role in the maintenance of epithelial characteristics.

show abstract

Section: Discussionmentioning

confidence: 99%

Plasma membrane phosphatidylinositol (4,5)-bisphosphate is critical for determination of epithelial characteristics

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Notably, Moesin, which outlines PAACs in confocal micrographs (Fig. 3 and Video 3), is a marker of microvilli in other Drosophila epithelia (Edwards et al, 1997; Lattner et al, 2019). We also found sausage-shaped (allantoid) ultrastructures that, like the ellipsoids, are lined with dense microvilli and circumscribed by SJs (Fig.…”

Section: Resultsmentioning

confidence: 96%

Progenitor cell integration into a barrier epithelium during adult organ turnover

Moreno-Roman

Galenza

et al. 2021

Preprint

View full text Add to dashboard Cite

Barrier epithelial organs face the constant challenge of sealing the interior body from the external environment while simultaneously replacing the cells that contact this environment. These replacement cells--the progeny of basal stem cells--are born without apical, barrier-forming structures such as a protective, lumen-facing membrane and occluding junctions. How stem cell progeny acquire these structures to become part of the barrier is unknown. Here we use Focused Ion Beam-Scanning Electron Microscopy (FIB-SEM), Correlative Light-Electron Microscopy (CLEM), and volumetric imaging of live and fixed organs to investigate progenitor integration in the intestinal epithelium of adult Drosophila. We find that stem cell daughters gestate their future lumenal-apical membrane beneath a transient, basal niche formed by an umbrella-shaped occluding junction that shelters the growing cell and adheres it to mature neighbor cells. The umbrella junction both targets formation of a deep, microvilli-lined, apical invagination and closes it off from the contents of the gut lumen. When the growing cell is sufficiently mature, the umbrella junction retracts to expose this Pre-Assembled Apical Compartment (PAAC) to the gut lumen, thus incorporating the new cell into the intestinal barrier. When we block umbrella junctions, stem cell daughters grow and attempt to differentiate but fail to integrate; when we block cell growth, no umbrella junctions form, and daughters arrest in early differentiation. Thus, stem cell progeny build new barrier structures in the shelter of a transient niche, where they are protected from lumenal insults until they are prepared to withstand them. By coordinating this dynamic junctional niche with progenitor cell differentiation, a physiologically active epithelial organ incorporates new cells while upholding integrity of its barrier.

show abstract

“…Members of the Spectrin family have a supporting role in providing cellular architecture through interaction with phospholipids and actively promoting polymerization of F-actin (Juliano, Kimelberg et al 1971, Pinder, Bray et al 1975, Hardy and Schrier 1978. Moreover, the secretory activity of ductal organs has been shown to be facilitated by Spectrins (Lattner, Leng et al 2019) During Drosophila development and under physiological conditions, the pathway that involves Spectrins, Rac1 and Pak1 has been shown to be required for the maintenance of cell polarity while when deregulated, it leads to the formation of enlarged vesicles similar to the EnVs(Lee and Thomas 2011). Thus our results provide a possible link between the observed induction of CLPs in a range of tumors and the effects of Spectrins and their deregulation (Ackermann andBrieger 2019, Yang, Yang et al 2021).…”

Section: Discussionmentioning

confidence: 99%

Chitinase-like proteins promoting tumorigenesis through disruption of cell polarity via enlarged endosomal vesicles

Khalili

Kunc

Herbrich

et al. 2022

Preprint

View full text Add to dashboard Cite

Chitinase-like proteins (CLPs) are associated with tissue-remodelling and inflammation but also with several disorders, including fibrosis, atherosclerosis, allergies, and cancer. However, the CLP's role in tumors is far from clear. Here, we utilize Drosophila melanogaster to investigate the function of CLPs (imaginal disc growth factors; Idgf's) in RasV12 dysplastic salivary glands (SGs). We find one of the Idgf's members, Idgf3, to be transcriptionally induced in a tissue- and cell-autonomously manner in a Drosophila hypertrophic model for early tumor progression. Induction involves non-canonical JNK-signaling via a positive feedback loop mediated by reactive oxygen species (ROS). Moreover, Idgf3 accumulates in enlarged vesicles (EnVs) that promote tumor progression by disrupting cytoskeletal organization, independent of Rab5 and Rab11. The process is mediated via Rac1 and the downstream component,Spectrin, which localizes to the EnVs. Similar to Idgf3, expression of two human members of the CLP family in Drosophila SGs aggravates tumor-related phenotypes. Our data provide new insight into a phylogenetically conserved tissue-autonomous CLP function in tumors and identify specific targets for tumor control.

show abstract

Crumbs organizes the transport machinery by regulating apical levels of PI(4,5)P2 in Drosophila

Cited by 18 publications

References 214 publications

Plasma membrane phosphatidylinositol (4,5)-bisphosphate is critical for determination of epithelial characteristics

Plasma membrane phosphatidylinositol (4,5)-bisphosphate is critical for determination of epithelial characteristics

Progenitor cell integration into a barrier epithelium during adult organ turnover

Chitinase-like proteins promoting tumorigenesis through disruption of cell polarity via enlarged endosomal vesicles

Contact Info

Product

Resources

About