11 results on '"Lewellyn, Lindsay"'
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2. Misshapen decreases integrin levels to promote epithelial motility and planar polarity in Drosophila.
- Author
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Lewellyn, Lindsay, Cetera, Maureen, and Horne-Badovinac, Sally
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DROSOPHILA , *EPITHELIUM , *CELL migration , *CELLULAR mechanics , *PROTEIN kinases - Abstract
Complex organ shapes arise from the coordinate actions of individual cells. The Drosophila egg chamber is an organ-like structure that lengthens along its anterior-posterior axis as it grows. This morphogenesis depends on an unusual form of planar polarity in the organ's outer epithelial layer, the follicle cells. Interestingly, this epithelium also undergoes a directed migration that causes the egg chamber to rotate around its anterior-posterior axis. However, the functional relationship between planar polarity and migration in this tissue is unknown. We have previously reported that mutations in the Misshapen kinase disrupt follicle cell planar polarity. Here we show that Misshapen's primary role in this system is to promote individual cell motility. Misshapen decreases integrin levels at the basal surface, which may facilitate detachment of each cell's trailing edge. These data provide mechanistic insight into Misshapen's conserved role in cell migration and suggest that follicle cell planar polarity may be an emergent properly of individual cell migratory behaviors within the epithelium. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
3. The chromosomal passenger complex and centralspindlin independently contribute to contractile ring assembly.
- Author
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Lewellyn, Lindsay, Carvalho, Ana, Desai, Arshad, Maddox, Amy S., and Oegema, Karen
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CHROMOSOMAL proteins , *SPINDLE apparatus , *CYTOKINESIS , *CAENORHABDITIS elegans , *SEPTINS , *GUANOSINE triphosphatase - Abstract
The chromosomal passenger complex (CPC) and centralspindlin are conserved cytokinesis regulators that localize to the spindle midzone, which forms between the separating chromosomes. Previous work placed the CPC and centralspindlin in a linear pathway that governs midzone formation. Using Caenorhabditis elegans embryos, we test whether there is a similar linear relationship between centralspindlin and the CPC in contractile ring constriction during cytokinesis. We show that simultaneous inhibition of the CPC kinase Aurora BAIR-2 and the centralspindlin component MKLP1ZEN-4 causes an additive constriction defect. Consistent with distinct roles for the proteins, inhibition of filamentous septin guanosine triphosphatases alleviates constriction defects in Aurora BAIR-2-inhibited embryos, whereas inhibition of Rac does so in MKLP1ZEN-4-inhibited embryos. Centralspindlin and the CPC are not required to enrich ring proteins at the cell equator but instead regulate formation of a compact mature ring. Therefore, in contrast to the linear midzone assembly pathway, centralspindlin and the CPC make independent contributions to control transformation of the sheet-like equatorial band into a ribbon-like contractile ring at the furrow tip. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
4. Inhibition of Rac by the GAP Activity of Centralspindlin Is Essential for Cytokinesis.
- Author
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Canman, Julie C., Lewellyn, Lindsay, Laband, Kimberley, Smerdon, Stephen J., Desai, Arshad, Bowerman, Bruce, and Oegema, Karen
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CYTOKINESIS , *GUANOSINE triphosphatase , *MICROTUBULES , *CHROMOSOMES , *KINESIN , *ACTIVATION (Chemistry) - Abstract
During cytokinesis, the guanosine triphosphatase (GTPase) RhoA orchestrates contractile ring assembly and constriction. RhoA signaling is controlled by the central spindle, a set of microtubule bundles that forms between the separating chromosomes. Centralspindlin, a protein complex consisting of the kinesin-6 ZEN-4 and the Rho family GTPase activating protein (GAP) CYK-4, is required for central spindle assembly and cytokinesis in Coenorhabditis elegans. However, the importance of the CYK-4 GAP activity and whether it regulates RhoA remain unclear. We found that two separation-of-function mutations in the GAP domain of CYK-4 lead to cytokinesis defects that mimic centralspindlin loss of function. These defects could be rescued by depletion of the GTPase Rac or its effectors, but not by depletion of RhoA. Thus, inactivation of Rac by centralspindlin functions in parallel with RhoA activation to drive contractile ring constriction during cytokinesis. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
5. Anillin and the Septins Promote Asymmetric Ingression of the Cytokinetic Furrow
- Author
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Maddox, Amy Shaub, Lewellyn, Lindsay, Desai, Arshad, and Oegema, Karen
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CYTOKINESIS , *ACTIN , *MYOSIN , *G proteins , *OLIGOMERS , *CELL division , *CONTRACTILITY (Biology) , *SYMMETRY (Biology) - Abstract
Summary: During cytokinesis, constriction of a cortical contractile ring generates a furrow that partitions one cell into two. The contractile ring contains three filament systems: actin, bipolar myosin II filaments, and septins, GTP-binding hetero-oligomers that polymerize to form a membrane-associated lattice. The contractile ring also contains a potential filament crosslinker, Anillin, that binds all three filament types. Here, we show that the contractile ring possesses an intrinsic symmetry-breaking mechanism that promotes asymmetric furrowing. Asymmetric ingression requires Anillin and the septins, which promote the coalescence of components on one side of the contractile ring, but is insensitive to a 10-fold reduction in myosin II levels. When asymmetry is disrupted, cytokinesis becomes sensitive to partial inhibition of contractility. Thus, asymmetric furrow ingression, a prevalent but previously unexplored feature of cell division in metazoans, is generated by the action of two conserved furrow components and serves a mechanical function that makes cytokinesis robust. [Copyright &y& Elsevier]
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- 2007
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6. Precise levels of the Drosophila adaptor protein Dreadlocks maintain the size and stability of germline ring canals.
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Stark, Kara, Crowe, Olivia, and Lewellyn, Lindsay
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ADAPTOR proteins , *GERM cells , *DROSOPHILA , *CELL anatomy , *FRUIT flies - Abstract
Intercellular bridges are essential for fertility in many organisms. The developing fruit fly egg has become the premier model system to study intercellular bridges. During oogenesis, the oocyte is connected to supporting nurse cells by relatively large intercellular bridges, or ring canals. Once formed, the ring canals undergo a 20- fold increase in diameter to support the movement of materials from the nurse cells to the oocyte. Here, we demonstrate a novel role for the conserved SH2/SH3 adaptor protein Dreadlocks (Dock) in regulating ring canal size and structural stability in the germline. Dock localizes at germline ring canals throughout oogenesis. Loss of Dock leads to a significant reduction in ring canal diameter, and overexpression of Dock causes dramatic defects in ring canal structure and nurse cell multinucleation. The SH2 domain of Dock is required for ring canal localization downstream of Src64 (also known as Src64B), and the function of one or more of the SH3 domains is necessary for the strong overexpression phenotype. Genetic interaction and localization studies suggest that Dock promotes WASp-mediated Arp2/3 activation in order to determine ring canal size and regulate growth. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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7. The Misshapen kinase regulates the size and stability of the germline ring canals in the Drosophila egg chamber.
- Author
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Kline, Ashley, Curry, Travis, and Lewellyn, Lindsay
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DROSOPHILA , *INSECT reproduction , *EGGS , *GERM cells , *ACTIN , *CYTOSKELETON , *CARRIER proteins , *PHYSIOLOGY - Abstract
Intercellular bridges are conserved structures that allow neighboring cells to exchange cytoplasmic material; defects in intercellular bridges can lead to infertility in many organisms. Here, we use the Drosophila egg chamber to study the mechanisms that regulate intercellular bridges. Within the developing egg chamber, the germ cells (15 nurse cells and 1 oocyte) are connected to each other through intercellular bridges called ring canals, which expand over the course of oogenesis to support the transfer of materials from the nurse cells to the oocyte. The ring canals are enriched in actin and actin binding proteins, and many proteins have been identified that localize to the germline ring canals and control their expansion and stability. Here, we demonstrate a novel role for the Ste20 family kinase, Misshapen (Msn), in regulation of the size of the germline ring canals. Msn localizes to ring canals throughout most of oogenesis, and depletion of Msn led to the formation of larger ring canals. Over-expression of Msn decreased ring canal diameter, and expression of a membrane tethered form of Msn caused ring canal detachment and nurse cell fusion. Altering the levels or localization of Msn also led to changes in the actin cytoskeleton and altered the localization of E-cadherin, which suggests that Msn could be indirectly limiting ring canal size by altering the structure or dynamics of the actin cytoskeleton and/or adherens junctions. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
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8. The Misshapen kinase negatively regulates integrin levels to promote collective cell migration in Drosophila
- Author
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Horne-Badovinac, Sally and Lewellyn, Lindsay
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- 2011
- Full Text
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9. The Arp2/3 complex and the formin, Diaphanous, are both required to regulate the size of germline ring canals in the developing egg chamber.
- Author
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Thestrup, Josephine, Tipold, Marina, Kindred, Alexandra, Stark, Kara, Curry, Travis, and Lewellyn, Lindsay
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MICROFILAMENT proteins , *SOMATIC cells , *FRUIT flies , *EGGS , *BIRD eggs - Abstract
Intercellular bridges are an essential structural feature found in both germline and somatic cells throughout the animal kingdom. Because of their large size, the germline intercellular bridges, or ring canals, in the developing fruit fly egg chamber are an excellent model to study the formation, stabilization, and growth of these structures. Within the egg chamber, the germline ring canals connect 15 supporting nurse cells to the developing oocyte, facilitating the transfer of materials required for successful oogenesis. The ring canals are derived from a stalled actomyosin contractile ring; once formed, additional actin and actin-binding proteins are recruited to the ring to support the 20-fold growth that accompanies oogenesis. These behaviors provide a unique model system to study the actin regulators that control incomplete cytokinesis, intercellular bridge formation, and growth. By temporally controlling their expression in the germline, we have demonstrated that the Arp2/3 complex and the formin, Diaphanous (Dia), coordinately regulate ring canal size and growth throughout oogenesis. Dia is required for successful incomplete cytokinesis and the initial stabilization of the germline ring canals. Once ring canals have formed, the Arp2/3 complex and Dia cooperate to determine ring canal size and maintain stability. Our data suggest that nurse cells must maintain a precise balance between the activity of these two nucleators during oogenesis. Image 1 • Depletion of ArpC2 leads to variation in ring canal size throughout oogenesis. • Diaphanous is required for incomplete cytokinesis and to limit ring canal expansion. • Expression of an activated Diaphanous produces smaller, lumenless ring canals. • Reducing Diaphanous provides a modest rescue of the arpC2-RNAi phenotype. • Once formed, the Arp2/3 complex and Diaphanous coordinately regulate ring canal size. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
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10. The midbody ring scaffolds the abscission machinery in the absence of midbody microtubules.
- Author
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Green, Rebecca A., Mayers, Jonathan R., Shaohe Wang, Lewellyn, Lindsay, Desai, Arshad, Audhya, Anjon, and Oegema, Karen
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ABSCISSION (Botany) , *CYTOPLASM , *CELL division , *MICROTUBULES , *CELL proliferation , *CAENORHABDITIS elegans - Abstract
Abscission completes cytokinesis to form the two daughter cells. Although abscission could be organized from the inside out by the microtubule-based midbody or from the outside in by the contractile ring-derived midbody ring, it is assumed that midbody microtubules scaffold the abscission machinery. In this paper, we assess the contribution of midbody microtubules versus the midbody ring in the Caenorhabditis elegans embryo. We show that abscission occurs in two stages. First, the cytoplasm in the daughter cells becomes isolated, coincident with formation of the intercellular bridge; proper progression through this stage required the septins (a midbody ring component) but not the membrane-remodeling endosomal sorting complex required for transport (ESCRT) machinery. Second, the midbody and midbody ring are released into a specific daughter cell during the subsequent cell division; this stage required the septins and the ESCRT machinery. Surprisingly, midbody microtubules were dispensable for both stages. These results delineate distinct steps during abscission and highlight the central role of the midbody ring, rather than midbody microtubules, in their execution. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
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11. Dephosphorylation of the Ndc80 Tail Stabilizes Kinetochore-Microtubule Attachments via the Ska Complex.
- Author
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Cheerambathur, Dhanya K., Prevo, Bram, Hattersley, Neil, Lewellyn, Lindsay, Corbett, Kevin D., Oegema, Karen, and Desai, Arshad
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CELL division , *DEPHOSPHORYLATION , *KINETOCHORE , *MICROTUBULES , *AURORA kinases , *CAENORHABDITIS elegans - Abstract
Summary During cell division, genome inheritance is orchestrated by microtubule attachments formed at kinetochores of mitotic chromosomes. The primary microtubule coupler at the kinetochore, the Ndc80 complex, is regulated by Aurora kinase phosphorylation of its N-terminal tail. Dephosphorylation is proposed to stabilize kinetochore-microtubule attachments by strengthening electrostatic interactions of the tail with the microtubule lattice. Here, we show that removal of the Ndc80 tail, which compromises in vitro microtubule binding, has no effect on kinetochore-microtubule attachments in the Caenorhabditis elegans embryo. Despite this, preventing Aurora phosphorylation of the tail results in prematurely stable attachments that restrain spindle elongation. This premature stabilization requires the conserved microtubule-binding Ska complex, which enriches at attachment sites prior to anaphase onset to dampen chromosome motion. We propose that Ndc80-tail dephosphorylation promotes stabilization of kinetochore-microtubule attachments via the Ska complex and that this mechanism ensures accurate segregation by constraining chromosome motion following biorientation on the spindle. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
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