Neuralized regulates Crumbs endocytosis and epithelium morphogenesis via specific Stardust isoforms

Perez-Mockus, Gantas; Roca, Vanessa; Mazouni, Khalil; Schweisguth, François

doi:10.1083/jcb.201611196

Cited by 36 publications

(82 citation statements)

References 70 publications

(127 reference statements)

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“…This is in contrast to Crb, as we find that in the pupal photoreceptor, approximately 40% is mobile over the same time span. This difference is likely to reflect that the Crb-Par6 interaction is dynamic and also that Crb turnover depends at least in part 395 on endocytosis and recycling, which might operate at longer time scales (Lin et al, 2015;Perez-Mockus et al, 2017). We also find that when compared to the pupal photoreceptor, in the follicular epithelium a greater proportion of Crb is mobile (60%), indicating that differences exist between these two tissues when considering the relative stability of Crb.…”

mentioning

confidence: 76%

Cdc42 promotes epithelial morphogenesis by coupling Par-complex and Crumbs recruitment via Par6-aPKC

Almeida

Walther

Pressé

et al. 2019

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confidence: 76%

Cdc42 promotes epithelial morphogenesis by coupling Par-complex and Crumbs recruitment via Par6-aPKC

Almeida

Walther

Pressé

et al. 2019

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“…In addition, further complexity regarding the role of crb stems from recent findings revealing that Neur, an E3 ligase critical for Dl endocytosis Lai et al, 2001;Pavlopoulos et al, 2001;Yeh et al, 2001), also controls the stability of Sdt, and thereby affects Crb protein levels (Perez-Mockus et al, 2017). It is tempting to speculate that Notch OFF cells (NBs), which maintain proneural gene expression and hence activate neur expression, will have increased Neur, and hence increased endocytosis of Sdt, and thereby decreased Crb levels, leading to reduced Notch receptor activation.…”

Section: Interplay Of Crb Notch Signalling Soxn and Wor During Nb Smentioning

confidence: 99%

“…Moreover, studies reveal that the EMT and apical polarity gene crumbs (crb) modulates Notch signalling (Das and Knust, 2018;Richardson and Pichaud, 2010). Intriguingly, recent findings show that Neur not only regulates Dl endocytosis, but also regulates Crb endocytosis, by controlling Stardust (Sdt) stability (another EMT and apical polarity gene; Pals1 in mammals) (Perez-Mockus et al, 2017). These findings suggest an intimate interplay between Notch signalling and some key EMT genes.…”

Section: Introductionmentioning

confidence: 99%

DrosophilaNeuroblast Selection Gated by Notch, Snail, SoxB and EMT Gene Interplay

Arefin

Parvin

Bahrampour

et al. 2019

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In the developing Drosophila central nervous system neural progenitor (neuroblast; NB) selection is gated by lateral inhibition, controlled by Notch signalling and proneural genes. However, proneural mutants only display partial NB reduction, indicating the existence of additional genes with proneural activity. In addition, recent studies reveal involvement of key epithelial-mesenchymal transition (EMT) genes in NB selection, but the regulatory interplay between Notch signalling and the EMT machinery is unclear. We find that the SoxB gene SoxNeuro and the Snail gene worniou are integrated with the Notch pathway, and constitute the missing proneural genes. Notch signalling, the proneural, SoxNeuro, and worniou genes regulate key EMT genes to orchestrate the NB specification process. Hence, we uncover an expanded lateral inhibition network for NB specification, and demonstrate its link to key players in the EMT machinery. Because of the evolutionary conservation of the genes involved, the Notch-SoxB-Snail-EMT network may control neural progenitor selection in many other systems.

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“…Similar phenotypes have been reported in mouse embryos mutant for Crb2 or Crb3 (Charrier et al, 2015; Szymaniak et al, 2015; Whiteman et al, 2014; Xiao et al, 2011; Ramkumar et al, 2016). In addition, Drosophila Crb has been associated with other functions, which are independent of its roles in epithelial integrity, such as regulation of tissue growth via the Hippo pathway, regulation of Notch signaling (Das and Knust, 2018; Nemetschke and Knust, 2016; Perez-Mockus et al, 2017; Herranz et al, 2006), as well as photoreceptor morphogenesis and survival under light stress (reviewed in (Pocha and Knust, 2013; Bulgakova and Knust, 2009; Genevet and Tapon, 2011)).…”

Section: Introductionmentioning

confidence: 99%

Crumbs organizes the transport machinery by regulating apical levels of PI(4,5)P₂inDrosophila

Lattner

Leng

Knust

et al. 2019

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28An efficient vectorial intracellular transport machinery depends on a well-established apico-29 basal polarity and is a prerequisite for the function of secretory epithelia. Despite extensive 30 knowledge on individual trafficking pathways, little is known about the mechanisms 31 coordinating their temporal and spatial regulation. Here, we report that the polarity protein 32 Crumbs is essential for apical plasma membrane phospholipid-homeostasis and efficient 33 apical secretion. Through recruiting Heavy-Spectrin and MyosinV to the apical membrane, 34 Crumbs maintains the Rab6-, Rab11-and Rab30-dependent trafficking and regulates the lipid 35 phosphatases Pten and Ocrl. Crumbs knock-down results in increased apical levels of 36 PI(4,5)P2 and formation of a novel, Moesin-and PI(4,5)P2-enriched apical membrane sac 37 containing microvilli-like structures. Our results identify Crumbs as an essential hub required 38 to maintain the organization of the apical membrane and the physiological activity of the larval 39 salivary gland. 40 41 Epithelia can organize as layers or tubes, which form barriers and thus separate 43 internal biological compartments from the environment. Many epithelia are specialized for 44 absorption or secretion by performing selective and directional transport of nutrients, enzymes 45 and waste products, which is essential for metazoan life (Cereijido et al., 2004; Rodriguez-46 Boulan and Macara, 2014; Lemaitre and Miguel-Aliaga, 2013). To perform these functions, 47 epithelial cells are highly polarized: plasma membrane proteins and lipids are distributed 48 asymmetrically into an apical domain facing the environment or a lumen, and a basolateral 49 domain that contacts the neighboring cell and/or a basal lamina. In addition, polarity is 50 manifested by uneven distribution of organelles, asymmetric cytoskeleton organization and 51 directed trafficking (Rodriguez-Boulan and Macara, 2014; Knust and Bossinger, 2002; Eaton 52 and Martin-Belmonte, 2014). The latter is particularly obvious in secretory epithelia, for 53 example the salivary glands, which produce vast amounts of material that is secreted into the 54 gland lumen (Blasky et al., 2015; Iruela-Arispe and Beitel, 2013; Eaton and Martin-Belmonte, 55 2014; Chung et al., 2014; Miguel-Aliaga et al., 2018).56 Several evolutionarily conserved proteins regulate epithelial cell polarity. These include 57 members of the apical Crumbs-and PAR-complexes, and the basolateral Scrib-Dlg-Lgl 58 module (reviewed in (Flores-Benitez and Knust, 2016; Roman-Fernandez and Bryant, 2016)). 59The Crumbs (Crb) protein has a large extracellular domain (>2000 aa), and a small intracellular 60 domain (37 aa) (Tepass et al., 1990; Wodarz et al., 1993), which harbors two protein-protein 61 interaction motifs, a C-terminal PDZ (Postsynaptic density/Discs large/ZO-1)-domain binding 62 motif (PBM) and a juxtamembrane FERM (protein 4.1/ezrin/radixin/moesin)-domain binding 63 motif (FBM). The PBM is important for cell polarity and can bind Stardust (Sdt) and Par-6 (Li

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Neuralized regulates Crumbs endocytosis and epithelium morphogenesis via specific Stardust isoforms

Abstract: The E3 ubiquitin ligase Neuralized is shown to interact with a subset of the Stardust isoforms to regulate the endocytosis of the apical protein Crumbs and thereby promote epithelial remodeling during Drosophila development.

Cited by 36 publications

References 70 publications

Cdc42 promotes epithelial morphogenesis by coupling Par-complex and Crumbs recruitment via Par6-aPKC

Cdc42 promotes epithelial morphogenesis by coupling Par-complex and Crumbs recruitment via Par6-aPKC

DrosophilaNeuroblast Selection Gated by Notch, Snail, SoxB and EMT Gene Interplay

Crumbs organizes the transport machinery by regulating apical levels of PI(4,5)P₂inDrosophila

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Neuralized regulates Crumbs endocytosis and epithelium morphogenesis via specific Stardust isoforms

Abstract: The E3 ubiquitin ligase Neuralized is shown to interact with a subset of the Stardust isoforms to regulate the endocytosis of the apical protein Crumbs and thereby promote epithelial remodeling during Drosophila development.

Cited by 36 publications

References 70 publications

Cdc42 promotes epithelial morphogenesis by coupling Par-complex and Crumbs recruitment via Par6-aPKC

Cdc42 promotes epithelial morphogenesis by coupling Par-complex and Crumbs recruitment via Par6-aPKC

DrosophilaNeuroblast Selection Gated by Notch, Snail, SoxB and EMT Gene Interplay

Crumbs organizes the transport machinery by regulating apical levels of PI(4,5)P2inDrosophila

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Crumbs organizes the transport machinery by regulating apical levels of PI(4,5)P₂inDrosophila