scholarly journals Sro7 and Sro77, the yeast homologues of the Drosophila lethal giant larvae (Lgl), regulate cell proliferation via the Rho1–Tor1 pathway

Microbiology ◽  
2014 ◽  
Vol 160 (10) ◽  
pp. 2208-2214 ◽  
Author(s):  
Liang-Chun Liou ◽  
Qun Ren ◽  
Qiuqiang Gao ◽  
Zhaojie Zhang

Saccharomyces cerevisiae Sro7 and Sro77 are homologues of the Drosophila tumour suppressor lethal giant larvae (Lgl), which regulates cell polarity in Drosophila epithelial cells. Here, we showed that double mutation of SRO7/SRO77 was defective in colony growth. The colony of the SRO7/SRO77 double deletion was much smaller than the WT and appeared to be round with a smooth surface, compared with the WT. Analysis using transmission electron microscopy revealed multiple defects of the colony cells, including multiple budding, multiple nuclei, cell lysis and dead cells, suggesting that the double deletion caused defects in cell polarity and cell wall integrity (CWI). Overexpression of RHO1, one of the central regulators of cell polarity and CWI, fully recovered the sro7Δ/sro77Δ phenotype. We further demonstrated that sro7Δ/sro77Δ caused a decrease of the GTP-bound, active Rho1, which in turn caused an upregulation of TOR1. Deletion of TOR1 in sro7Δ/sro77Δ (sro7Δ/sro77Δ/tor1Δ) recovered the cell growth and colony morphology, similar to WT. Our results suggested that the tumour suppressor homologue SRO7/SRO77 regulated cell proliferation and yeast colony development via the Rho1–Tor1 pathway.

2003 ◽  
Vol 163 (5) ◽  
pp. 1089-1098 ◽  
Author(s):  
Melissa M. Rolls ◽  
Roger Albertson ◽  
Hsin-Pei Shih ◽  
Cheng-Yu Lee ◽  
Chris Q. Doe

Cell polarity is essential for generating cell diversity and for the proper function of most differentiated cell types. In many organisms, cell polarity is regulated by the atypical protein kinase C (aPKC), Bazooka (Baz/Par3), and Par6 proteins. Here, we show that Drosophila aPKC zygotic null mutants survive to mid-larval stages, where they exhibit defects in neuroblast and epithelial cell polarity. Mutant neuroblasts lack apical localization of Par6 and Lgl, and fail to exclude Miranda from the apical cortex; yet, they show normal apical crescents of Baz/Par3, Pins, Inscuteable, and Discs large and normal spindle orientation. Mutant imaginal disc epithelia have defects in apical/basal cell polarity and tissue morphology. In addition, we show that aPKC mutants show reduced cell proliferation in both neuroblasts and epithelia, the opposite of the lethal giant larvae (lgl) tumor suppressor phenotype, and that reduced aPKC levels strongly suppress most lgl cell polarity and overproliferation phenotypes.


2019 ◽  
Vol 116 (22) ◽  
pp. 10804-10812 ◽  
Author(s):  
Lior Almagor ◽  
Ivan S. Ufimtsev ◽  
Aruna Ayer ◽  
Jingzhi Li ◽  
William I. Weis

Metazoan cell polarity is controlled by a set of highly conserved proteins. Lethal giant larvae (Lgl) functions in apical-basal polarity through phosphorylation-dependent interactions with several other proteins as well as the plasma membrane. Phosphorylation of Lgl by atypical protein kinase C (aPKC), a component of the partitioning-defective (Par) complex in epithelial cells, excludes Lgl from the apical membrane, a crucial step in the establishment of epithelial cell polarity. We present the crystal structures of human Lgl2 in both its unphosphorylated and aPKC-phosphorylated states. Lgl2 adopts a double β-propeller structure that is unchanged by aPKC phosphorylation of an unstructured loop in its second β-propeller, ruling out models of phosphorylation-dependent conformational change. We demonstrate that phosphorylation controls the direct binding of purified Lgl2 to negative phospholipids in vitro. We also show that a coil–helix transition of this region that is promoted by phosphatidylinositol 4,5-bisphosphate (PIP2) is also phosphorylation-dependent, implying a highly effective phosphorylative switch for membrane association.


2021 ◽  
Author(s):  
Pénélope Darnat ◽  
Angelique Burg ◽  
Jérémy Sallé ◽  
Jérôme Lacoste ◽  
Sophie Louvet-Vallée ◽  
...  

Abstract Cell proliferation and cell polarity need to be precisely coordinated to orient the asymmetric cell divisions crucial for generating cell diversity in epithelia. In many instances, the Frizzled/Dishevelled planar cell polarity pathway is involved in mitotic spindle orientation, but how this is spatially and temporally coordinated with cell cycle progression has remained elusive. Using Drosophila sensory organ precursor cells as a model system, we show that Cyclin A, the main Cyclin driving the transition to M-phase of the cell cycle, is recruited to the apical-posterior cortex in prophase by the Frizzled/Dishevelled complex. This cortically localized Cyclin A then regulates the orientation of the division by recruiting Mud, a homologue of NuMA, the well-known spindle-associated protein. The observed non-canonical subcellular localization of Cyclin A reveals this mitotic factor as a direct link between cell proliferation, cell polarity and spindle orientation.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jukka Intosalmi ◽  
Adrian C. Scott ◽  
Michelle Hays ◽  
Nicholas Flann ◽  
Olli Yli-Harja ◽  
...  

Abstract Background Multicellular entities like mammalian tissues or microbial biofilms typically exhibit complex spatial arrangements that are adapted to their specific functions or environments. These structures result from intercellular signaling as well as from the interaction with the environment that allow cells of the same genotype to differentiate into well-organized communities of diversified cells. Despite its importance, our understanding how this cell–cell and metabolic coupling lead to functionally optimized structures is still limited. Results Here, we present a data-driven spatial framework to computationally investigate the development of yeast colonies as such a multicellular structure in dependence on metabolic capacity. For this purpose, we first developed and parameterized a dynamic cell state and growth model for yeast based on on experimental data from homogeneous liquid media conditions. The inferred model is subsequently used in a spatially coarse-grained model for colony development to investigate the effect of metabolic coupling by calibrating spatial parameters from experimental time-course data of colony growth using state-of-the-art statistical techniques for model uncertainty and parameter estimations. The model is finally validated by independent experimental data of an alternative yeast strain with distinct metabolic characteristics and illustrates the impact of metabolic coupling for structure formation. Conclusions We introduce a novel model for yeast colony formation, present a statistical methodology for model calibration in a data-driven manner, and demonstrate how the established model can be used to generate predictions across scales by validation against independent measurements of genetically distinct yeast strains.


2013 ◽  
Vol 740-742 ◽  
pp. 435-438
Author(s):  
Hui Deng ◽  
Kazuya Yamamura

Plasma-assisted polishing (PAP) was proposed for finishing difficult-to-machine materials, such as single-crystal SiC, reaction-sintered SiC, diamond, and sapphire. In the case of PAP application to the finishing of the 4H-SiC surface, an atomically smooth surface without any scratches was obtained. In this study, we observed 4H-SiC (0001) surfaces processed by water vapor plasma oxidation and PAP using ceria abrasives through cross-sectional transmission electron microscopy (XTEM). Water vapor plasma oxidation was conducted for 1 min, 5 min and 60 min. An intermediate layer located between SiO2 and SiC, which corresponds to silicon oxycarbide, was clearly observed in the case of a short oxidation. As oxidation time increased from 1 min to 60 min, average oxidation rate decreased from 2.7 nm/min to 0.6 nm/min. An atomically smooth 4H-SiC (0001) surface was obtained after PAP for 60 min using ceria abrasives.


2016 ◽  
Vol 5 (6) ◽  
Author(s):  
Tuong Vi Tran ◽  
Uyen Vy Vo ◽  
Dong Yen Pham ◽  
Dai Lam Tran ◽  
Thi Hiep Nguyen ◽  
...  

AbstractPorous nanosilica (PNS) has been attracting much attention in fabrication of nanocarriers for a drug delivery system (DDS). However, the unmodified PNS-based carriers exhibited a significant initial burst release of drug, which may limit their potential clinical application. In this study, PNS was surface conjugated with cyclodextrin (CD) which was functionalized with adamantylamine-polyethylene glycol (APEG) for 5-fluorouracil (5-FU) delivery, in which case CD was used due to its ability to form a stable inclusion complex with 5-FU and APEG. The conjugated PNS (PNSC@APEG) was successfully prepared with spherical shape and diameter around 50 nm, determined by transmission electron microscopy (TEM). In addition, 5-FU was efficiently trapped in PNSC@APEG particles, which were around 63.4%±3.8% and was slowly released up to 3 days in phosphate buffer saline (PBS). Furthermore, the cell proliferation kit I (MTT) assay data showed that PNSC@APEG was a biocompatible nanocarrier. These results indicated that PNSC@APEG nanoparticles have a great potential as novel carriers for anticancer drug delivery.


BioEssays ◽  
2003 ◽  
Vol 25 (6) ◽  
pp. 542-553 ◽  
Author(s):  
Patrick Humbert ◽  
Sarah Russell ◽  
Helena Richardson

Oncogene ◽  
2004 ◽  
Vol 23 (53) ◽  
pp. 8688-8694 ◽  
Author(s):  
Daniela Grifoni ◽  
Flavio Garoia ◽  
Christoph C Schimanski ◽  
Gösta Schmitz ◽  
Elisa Laurenti ◽  
...  

2008 ◽  
Vol 47-50 ◽  
pp. 367-370
Author(s):  
Guang Zhu ◽  
Xiao Ping Zou ◽  
Jin Cheng ◽  
Mao Fa Wang ◽  
Yi Su

The straight Y-shaped silica nanorods have been synthesized on Si wafer by thermal chemical evaporation of mixed powders of silica and graphite at 1300°C and condensation on Si substrate without assistance of any catalyst. The synthesized samples were characterized by means of scanning electron microscopy, transmission electron microscopy. The results suggested that the straight Y-shaped silica nanorods have uniform diameter about 50-200nm and neat smooth surface. The growth of such silica nanorods may be a result of the fluctuation of external conditions causing a change in the growth direction of silica nanorods developed.


1967 ◽  
Vol 125 (4) ◽  
pp. 703-720 ◽  
Author(s):  
J. L. Curry ◽  
J, J. Trentin ◽  
N. Wolf

The polycythemic repression of erythropoiesis and the restoration of erythropoiesis by specific stimulation were studied in the spleen colony system in irradiated mice. 1. A 5 day period of erythropoietin stimulation (exogenous erythropoietin) or repression (polycythemia) of the bone marrow donor only, does not significantly alter the number or type of colonies formed by the transplanted marrow cells. 2. Erythropoietin stimulation did not alter the number or type of endogenous colonies formed in mice receiving 580 R. Erythropoietin repression (polycythemia) markedly reduced the growth but not the number of erythroid colonies, while not affecting the other types of colonies formed endogenously. 3. Erythropoietin stimulation of the irradiated recipient during colony growth did not alter the number or type of spleen colonies formed by transplanted marrow. Erythropoietin repression by polycythemia during colony growth completely suppressed the appearance of morphologically erythroid colonies without significantly altering the incidence of the other colony types. This effect of polycythemia was completely prevented by exogenous erythropoietin. Irradiated mice are therefore presumed to be secreting sufficient erythropoietin for maximal erythroid colony development. 4. The erythroid colonies suppressed by polycythemia were recognizable as microscopic foci of undifferentiated cells. Exposure of these foci to erythropoietin stimulation at different periods in their development was manifested by different degrees of growth and differentiation, from which it is apparent that erythropoietin stimulates not only morphological differentiation but also rapid mitosis. Retransplantation of either erythroid or of neutrophilic primary spleen colonies gave rise to both erythroid and neutrophilic secondary spleen colonies. The percentage of erythroid secondary colonies was slightly but significantly higher among the progeny of transplanted erythroid primary colonies than among the progeny of transplanted neutrophilic primary colonies. On the basis of these and other results, a working hypothesis is proposed for factors controlling the growth and differentiation of spleen colonies from transplanted bone marrow. It is postulated that most but perhaps not all spleen colony-forming units are pluripotent hemopoietic stem cells. It is further postulated that hemopoietic-inductive microenvironments (HIM) of different kinds exist in both the spleen and the bone marrow, and that these determine the differentiation of pluripotent stem cells into each of the lines of hemopoietic differentiation. Erythropoietin therefore may "induce" erythroid differentiation of only those stem cells under the influence of an erythroid HIM. Alternatively erythropoietin may act only as a growth and function stimulant of those stem cells that have been "induced" by an erythroid HIM into a state of erythropoietin responsiveness. In the latter case morphological differentiation presumably results from the functional activity stimulated by ESF.


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