scholarly journals A Rich1/Amot Complex Regulates the Cdc42 GTPase and Apical-Polarity Proteins in Epithelial Cells

Cell ◽  
2006 ◽  
Vol 125 (3) ◽  
pp. 535-548 ◽  
Author(s):  
Clark D. Wells ◽  
James P. Fawcett ◽  
Andreas Traweger ◽  
Yojiro Yamanaka ◽  
Marilyn Goudreault ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Apical Polarity ◽  
Polarity Proteins

scholarly journals Electrostatic plasma membrane targeting contributes to Dlg function in cell polarity and tumorigenesis

Development ◽  
2021 ◽  
pp. dev.196956
Author(s):  
Juan Lu ◽  
Wei Dong ◽  
Yan Tao ◽  
Yang Hong
Keyword(s):  
Plasma Membrane ◽  
Tumor Suppressor ◽  
Epithelial Cells ◽  
Cell Polarity ◽  
Significant Role ◽  
Discs Large ◽  
Cortical Localization ◽  
Polarity Proteins ◽  
Positively Charged

Discs large (Dlg) is an essential polarity protein and a tumor suppressor originally characterized in Drosophila but is also well conserved in vertebrates. Like the majority of polarity proteins, plasma membrane (PM)/cortical localization of Dlg is required for its function in polarity and tumorigenesis, but the exact mechanisms targeting Dlg to PM remain to be fully elucidated. Here we show that, similar to the recently discovered polybasic polarity proteins such as Lgl and aPKC, Dlg also contains a positively charged polybasic domain that electrostatically binds the PM phosphoinositides PI4P and PI(4,5)P2. Electrostatic targeting by the polybasic domain contributes significantly to the PM localization of Dlg in follicular and early embryonic epithelial cells, and is crucial for Dlg to regulate both polarity and tumorigenesis. The electrostatic PM targeting of Dlg is controlled by a potential phosphorylation-dependent allosteric regulation of its polybasic domain, and is specifically enhanced by the interactions between Dlg and another basolateral polarity protein and tumor suppressor Scrib. Our studies highlight an increasingly significant role of electrostatic PM targeting of polarity proteins in regulating cell polarity.

scholarly journals The Basolateral Polarity Module Promotes Slit Diaphragm Formation in Drosophila Nephrocytes, a Model of Vertebrate Podocytes

2021 ◽  
pp. ASN.2020071050
Author(s):  
Michael Mysh ◽  
John S. Poulton
Keyword(s):  
Nephrotic Syndrome ◽  
Protein Trafficking ◽  
Cell Biology ◽  
Genetic Interaction ◽  
Intercellular Junctions ◽  
Protein Distribution ◽  
Genetic Manipulations ◽  
Apicobasal Polarity ◽  
Apical Polarity ◽  
Polarity Proteins

BackgroundPodocyte slit diaphragms (SDs) are intercellular junctions that function as size-selective filters, excluding most proteins from urine. Abnormalities in SDs cause proteinuria and nephrotic syndrome. Podocytes exhibit apicobasal polarity, which can affect fundamental aspects of cell biology, including morphology, intercellular junction formation, and asymmetric protein distribution along the plasma membrane. Apical polarity protein mutations cause nephrotic syndrome, and data suggest apical polarity proteins regulate SD formation. However, there is no evidence that basolateral polarity proteins regulate SDs. Thus, the role of apicobasal polarity in podocytes remains unclear.MethodsGenetic manipulations and transgenic reporters determined the effects of disrupting apicobasal polarity proteins in Drosophila nephrocytes, which have SDs similar to those of mammalian podocytes. Confocal and electron microscopy were used to characterize SD integrity after loss of basolateral polarity proteins, and genetic-interaction studies illuminated relationships among apicobasal polarity proteins.ResultsThe study identified four novel regulators of nephrocyte SDs: Dlg, Lgl, Scrib, and Par-1. These proteins comprise the basolateral polarity module and its effector kinase. The data suggest these proteins work together, with apical polarity proteins, to regulate SDs by promoting normal endocytosis and trafficking of SD proteins.ConclusionsGiven the recognized importance of apical polarity proteins and SD protein trafficking in podocytopathies, the findings connecting basolateral polarity proteins to these processes significantly advance our understanding of SD regulation.

scholarly journals Apical polarity proteins recruit the RhoGEF Cysts to promote junctional myosin assembly

2019 ◽  
Vol 218 (10) ◽  
pp. 3397-3414 ◽  
Author(s):  
Jordan T. Silver ◽  
Frederik Wirtz-Peitz ◽  
Sérgio Simões ◽  
Milena Pellikka ◽  
Dong Yan ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Rho Gtpase ◽  
Adherens Junctions ◽  
Nucleotide Exchange ◽  
Temporal Regulation ◽  
Apical Polarity ◽  
Polarity Proteins ◽  
Spatio Temporal ◽  
Crumbs Complex

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 resembles the mutant phenotype of the apical polarity regulator Crumbs. This phenotype can be suppressed by the loss of basolateral polarity proteins, suggesting that Cysts is an integral component of the apical polarity protein network. We demonstrate that Cysts is recruited to the apico-lateral membrane through interactions with the Crumbs complex and Bazooka/Par3. Cysts activates Rho1 at adherens junctions and stabilizes junctional myosin. Junctional myosin depletion is similar in Cysts- and Crumbs-compromised embryos. Together, our findings indicate that Cysts is a downstream effector of the Crumbs complex and links apical polarity proteins to Rho1 and myosin activation at adherens junctions, supporting junctional integrity and epithelial polarity.

scholarly journals Regulated and constitutive protein targeting can be distinguished by secretory polarity in thyroid epithelial cells.

1991 ◽  
Vol 112 (3) ◽  
pp. 365-376 ◽  
Author(s):  
P Arvan ◽  
J Lee
Keyword(s):  
Epithelial Cells ◽  
Protein Targeting ◽  
Secretory Protein ◽  
Residual Fraction ◽  
Secretory Proteins ◽  
Apical Surface ◽  
Epithelial Monolayers ◽  
Apical Polarity ◽  
Intracellular Storage

We have studied concurrent apical/basolateral and regulated/constitutive secretory targeting in filter-grown thyroid epithelial monolayers in vitro, by following the exocytotic routes of two newly synthesized endogenous secretory proteins, thyroglobulin (Tg) and p500. Tg is a regulated secretory protein as indicated by its acute secretory response to secretagogues. Without stimulation, pulse-labeled Tg exhibits primarily two kinetically distinct routes: less than or equal to 80% is released in an apical secretory phase which is largely complete by 6-10 h, with most of the remaining Tg retained in intracellular storage from which delayed apical discharge is seen. The rapid export observed for most Tg is unlikely to be because of default secretion, since its apical polarity is preserved even during the period (less than or equal to 10 h) when p500 is released basolaterally by a constitutive pathway unresponsive to secretagogues. p500 also exhibits a second, kinetically distinct secretory route: at chase times greater than 10 h, a residual fraction (less than or equal to 8%) of p500 is secreted with an apical preponderance similar to that of Tg. It appears that this fraction of p500 has failed to be excluded from the regulated pathway, which has a predetermined apical polarity. From these data we hypothesize that a targeting hierarchy may exist in thyroid epithelial cells such that initial sorting to the regulated pathway may be a way of insuring apical surface delivery from one of two possible exocytotic routes originating in the immature storage compartment.

scholarly journals New insights into the organization and regulation of the apical polarity network in mammalian epithelial cells

FEBS Journal ◽  
2021 ◽  
Author(s):  
Eleanor Martin ◽  
Rossana Girardello ◽  
Gunnar Dittmar ◽  
Alexander Ludwig
Keyword(s):  
Epithelial Cells ◽  
Apical Polarity

scholarly journals Electrostatic Plasma Membrane Targeting is Essential for Dlg Function in Cell Polarity and Tumorigenesis

2020 ◽  
Author(s):  
Juan Lu ◽  
Wei Dong ◽  
Yan Tao ◽  
Yang Hong
Keyword(s):  
Plasma Membrane ◽  
Tumor Suppressor ◽  
Epithelial Cells ◽  
Cell Polarity ◽  
Primary Mechanism ◽  
Discs Large ◽  
Cortical Localization ◽  
Polarity Proteins ◽  
Positively Charged

SUMMARYDiscs large (Dlg) is an essential polarity protein and a tumor suppressor originally characterized in Drosophila but is also well conserved in vertebrates. Like the majority of polarity proteins, plasma membrane (PM)/cortical localization of Dlg is required for its function in regulating apical-basal polarity and tumorigenesis, but the exact mechanisms targeting Dlg to PM remain to be unclear. Here we show that, similar to recently discovered polybasic polarity proteins such as Lgl and aPKC, Dlg also contains a positively charged polybasic domain that electrostatically binds the PM phosphoinositides PI4P and PI(4,5)P2. Electrostatic targeting by the polybasic domain acts as the primary mechanism localizing Dlg to the PM in follicular and early embryonic epithelial cells, and is crucial for Dlg to regulate both polarity and tumorigenesis. The electrostatic PM targeting of Dlg is controlled by a potential phosphorylation-dependent allosteric regulation of its polybasic domain, and is specifically enhanced by interactions between Dlg and another basolateral polarity protein and tumor suppressor Scrib. Our studies highlight an increasingly significant role of electrostatic PM targeting of polarity proteins in regulating cell polarity.

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

2019 ◽  
Author(s):  
Jordan T. Silver ◽  
Frederik Wirtz-Peitz ◽  
Sérgio Simões ◽  
Milena Pellikka ◽  
Dong Yan ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Rho Gtpase ◽  
Adherens Junctions ◽  
Coiled Coil ◽  
Terminal Region ◽  
Nucleotide Exchange ◽  
Apical Polarity ◽  
Polarity Proteins ◽  
Spatio Temporal

AbstractThe 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.

scholarly journals A contractile actomyosin network linked to adherens junctions by Canoe/afadin helps drive convergent extension

2011 ◽  
Vol 22 (14) ◽  
pp. 2491-2508 ◽  
Author(s):  
Jessica K. Sawyer ◽  
Wangsun Choi ◽  
Kuo-Chen Jung ◽  
Li He ◽  
Nathan J. Harris ◽  
...  
Keyword(s):  
Cell Shape ◽  
Shape Change ◽  
Adherens Junction ◽  
Tissue Level ◽  
The Body ◽  
Convergent Extension ◽  
Planar Polarity ◽  
Cell Shape Change ◽  
Apical Polarity ◽  
Polarity Proteins

Integrating individual cell movements to create tissue-level shape change is essential to building an animal. We explored mechanisms of adherens junction (AJ):cytoskeleton linkage and roles of the linkage regulator Canoe/afadin during Drosophila germband extension (GBE), a convergent-extension process elongating the body axis. We found surprising parallels between GBE and a quite different morphogenetic movement, mesoderm apical constriction. Germband cells have an apical actomyosin network undergoing cyclical contractions. These coincide with a novel cell shape change—cell extension along the anterior–posterior (AP) axis. In Canoe's absence, GBE is disrupted. The apical actomyosin network detaches from AJs at AP cell borders, reducing coordination of actomyosin contractility and cell shape change. Normal GBE requires planar polarization of AJs and the cytoskeleton. Canoe loss subtly enhances AJ planar polarity and dramatically increases planar polarity of the apical polarity proteins Bazooka/Par3 and atypical protein kinase C. Changes in Bazooka localization parallel retraction of the actomyosin network. Globally reducing AJ function does not mimic Canoe loss, but many effects are replicated by global actin disruption. Strong dose-sensitive genetic interactions between canoe and bazooka are consistent with them affecting a common process. We propose a model in which an actomyosin network linked at AP AJs by Canoe and coupled to apical polarity proteins regulates convergent extension.

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