<i>Drosophila</i> PATJ supports adherens junction stability by modulating Myosin light chain activity

Sen, Arnab; Nagy-Zsvér-Vadas, Zsanett; Krahn, Michael P.

doi:10.1083/jcb.2012060642006c

Cited by 17 publications

(11 citation statements)

References 77 publications

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“…Our biochemical data show that the Cyst C-terminal region is sufficient for interactions with the scaffolding protein Patj, which couples Cyst to the Crb-complex. Patj has been implicated as a myosin II activator in the embryo (Sen et al, 2012). Given our genetic and biochemical data it is likely that Crb, Patj and Cyst form a complex that organizes junctional actomyosin.…”

Section: Cyst Associates With the Cortex Through A Multifaceted Mechamentioning

confidence: 85%

“…Given our genetic and biochemical data it is likely that Crb, Patj and Cyst form a complex that organizes junctional actomyosin. However, as Patj is not essential for embryonic survival (Sen et al, 2012), Cyst may interact with additional binding partners within the Crb complex. Another apical binding partner for Cyst is Baz/Par3, a conclusion supported by several lines of evidence.…”

Section: Cyst Associates With the Cortex Through A Multifaceted Mechamentioning

confidence: 99%

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The RhoGEF Cysts couples apical polarity proteins to Rho and myosin activity at adherens junctions

Silver

Wirtz-Peitz²,

Simões

et al. 2019

Preprint

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The spatio-temporal regulation of small Rho GTPases is crucial for the dynamic stability of epithelial tissues. However, how RhoGTPase activity is controlled during development remains largely unknown. To explore the regulation of Rho GTPases in vivo we analyzed the Rho GTPase guanine nucleotide exchange factor (RhoGEF) Cysts, the Drosophila orthologue of mammalian p114RhoGEF, GEF-H1, p190RhoGEF, and AKAP-13. Loss of Cysts causes a phenotype that closely resemble the mutant phenotype of the apical polarity regulator Crumbs.This phenotype can be suppressed by the loss of basolateral polarity proteins suggesting that Cysts in an integral component of the apical polarity protein network. Cysts activates Rho at adherens junctions to promote junctional enrichment of myosin II, which requires the RhoGEF domain and the coiled-coil domain containing C-terminal region of Cysts. Cysts recruitment to the apico-lateral cortex depends on Crumbs and Bazooka/Par3 and requires multiple domains within Cysts including the C-terminal region. Together, our findings indicate that Cysts links apical polarity proteins to Rho1 and myosin activation at adherens junctions to support junctional and epithelial integrity in the Drosophila ectoderm.

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Section: Cyst Associates With the Cortex Through A Multifaceted Mechamentioning

confidence: 85%

Section: Cyst Associates With the Cortex Through A Multifaceted Mechamentioning

confidence: 99%

The RhoGEF Cysts couples apical polarity proteins to Rho and myosin activity at adherens junctions

Silver

Wirtz-Peitz²,

Simões

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…To explore the in vivo relevance of our findings, we generated transgenic flies expressing GFP-tagged Par6 under a constitutive promoter (30) and analyzed the embryos at stage 11 ( Fig. 3, A to D).…”

Section: The Pbm Is Functionally Redundant With the Pdz Domain In Parmentioning

confidence: 99%

Structural basis for the interaction between the cell polarity proteins Par3 and Par6

et al. 2018

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Polarity is a fundamental property of most cell types. The Par protein complex is a major driving force in generating asymmetrically localized protein networks and consists of atypical protein kinase C (aPKC), Par3, and Par6. Dysfunction of this complex causes developmental abnormalities and diseases such as cancer. We identified a PDZ domain-binding motif in Par6 that was essential for its interaction with Par3 in vitro and for Par3-mediated membrane localization of Par6 in cultured cells. In fly embryos, we observed that the PDZ domain-binding motif was functionally redundant with the PDZ domain in targeting Par6 to the cortex of epithelial cells. Our structural analyses by x-ray crystallography and NMR spectroscopy showed that both the PDZ1 and PDZ3 domains but not the PDZ2 domain in Par3 engaged in a canonical interaction with the PDZ domain-binding motif in Par6. Par3 thus has the potential to recruit two Par6 proteins simultaneously, which may facilitate the assembly of polarity protein networks through multivalent PDZ domain interactions.

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“…Next we examined how the loss of apical Patj could affect the germband ectodermal epithelium, and ultimately macrophage migration. Patj has been shown to bind the Myosin binding subunit (MBS) of Myosin phosphatase (Sen et al, 2012), which downregulates Myosin activity by decreasing its phosphorylation (Kimura et al, 1996;Lee and Treisman, 2004). Although no antibody for Myosin phosphatase exists, we were able to analyze the localization and levels of active Myosin in the ectoderm using an antibody that detects the mono-phosphorylated form of Myosin regulatory light chain (MRLC, sqh in Drosophila) (Zhang and Ward, 2011).…”

Section: Eiger Maintains Apical Patj To Regulate Myosin Activity In the Ectoderm Without Affecting Polarity During Macrophage Tissue Invamentioning

confidence: 99%

Drosophila TNF Modulates Tissue Tension in the Embryo to Facilitate Macrophage Invasive Migration

et al. 2018

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Migrating cells penetrate tissue barriers during development, inflammatory responses, and tumor metastasis. We study if migration in vivo in such three-dimensionally confined environments requires changes in the mechanical properties of the surrounding cells using embryonic Drosophila melanogaster hemocytes, also called macrophages, as a model. We find that macrophage invasion into the germband through transient separation of the apposing ectoderm and mesoderm requires cell deformations and reductions in apical tension in the ectoderm. Interestingly, the genetic pathway governing these mechanical shifts acts downstream of the only known tumor necrosis factor superfamily member in Drosophila, Eiger, and its receptor, Grindelwald. Eiger-Grindelwald signaling reduces levels of active Myosin in the germband ectodermal cortex through the localization of a Crumbs complex component, Patj (Pals-1-associated tight junction protein). We therefore elucidate a distinct molecular pathway that controls tissue tension and demonstrate the importance of such regulation for invasive migration in vivo.

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Drosophila PATJ supports adherens junction stability by modulating Myosin light chain activity

Cited by 17 publications

References 77 publications

The RhoGEF Cysts couples apical polarity proteins to Rho and myosin activity at adherens junctions

The RhoGEF Cysts couples apical polarity proteins to Rho and myosin activity at adherens junctions

Structural basis for the interaction between the cell polarity proteins Par3 and Par6

Drosophila TNF Modulates Tissue Tension in the Embryo to Facilitate Macrophage Invasive Migration

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