Identification and Characterization of a Small Molecule Inhibitor of Formin-Mediated Actin Assembly

Rizvi, Syed Alipayam; Neidt, Erin M.; Cui, Jiayue; Feiger, Zach; Skau, Colleen T.; Gardel, Margaret L.; Kozmin, Sergey A.; Kovar, David R.

doi:10.1016/j.chembiol.2009.10.006

Cited by 342 publications

(410 citation statements)

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“…We further examined this main defect, which might be related to contractile ring formation and thus straight actin nucleators (Barr and Gruneberg, 2007;Fededa and Gerlich, 2012). To determine whether formin proteins are involved in cleavage furrow closure during PBE, oocytes were treated with 100 mM SMIFH2, a specific inhibitor of the formin homology (FH) 2 domain (Rizvi et al, 2009). To avoid perturbation of GVBD and to ensure correct spindle formation, SMIFH2 treatment was performed after GVBD (30 minutes after the treatment with 1-MeAde).…”

Section: Resultsmentioning

confidence: 99%

The Mos-MAPK pathway regulates Diaphanous-related formin activity to drive cleavage furrow closure during polar body emission in starfish oocytes

Ucar

Tachibana

Kishimoto

2013

Journal of Cell Science

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SummaryMaintenance of spindle attachment to the cortex and formation of the cleavage furrow around the protruded spindle are essential for polar body extrusion (PBE) during meiotic maturation of oocytes. Although spindle movement to the cortex has been well-studied, how the spindle is maintained at the cortex during PBE is unknown. Here, we show that activation of Diaphanous-related formin mediated by mitogen-activated protein kinase (MAPK) is required for tight spindle attachment to the cortex and cleavage furrow closure during PBE in starfish (Asterina pectinifera) oocytes. A. pectinifera Diaphanous-related formin (ApDia) had a distinct localization in immature oocytes and was localized to the cleavage furrow during PBE. Inhibition of the Mos-MAPK pathway or the actin nucleating activity of formin homology 2 domain prevented cleavage furrow closure and resulted in PBE failure. In MEK/MAPK-inhibited oocytes, activation of ApDia by relief of its intramolecular inhibition restored PBE. In summary, this study elucidates a link between the Mos-MAPK pathway and Diaphanous-related formins, that is responsible for maintaining tight spindle attachment to the cortex and cleavage furrow closure during PBE.

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Section: Resultsmentioning

confidence: 99%

The Mos-MAPK pathway regulates Diaphanous-related formin activity to drive cleavage furrow closure during polar body emission in starfish oocytes

Ucar

Tachibana

Kishimoto

2013

Journal of Cell Science

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“…In addition, a recent study showed that NMII-rich actin arcs in the IS are derived from formin-mediated actin polymerization primarily in the lamellipodia (51). To test whether the activation of ROCK and formin mediates MT-actin interactions at the T-cell contact zone, we activated EB3-EGFP-and TagRFP-Tactin-expressing Jurkat cells on anti-CD3-coated coverslips in the presence of Y-27632 or the formin inhibitor SMIFH2 (15 μM) (52). SMIFH2 inhibits the actin polymerization activity of formins.…”

Section: Mt Network Forms a Radially Emanating Dynamic Array During Tmentioning

confidence: 99%

Dynamic microtubules regulate cellular contractility during T-cell activation

Hui

Upadhyaya

2017

Proc. Natl. Acad. Sci. U.S.A.

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T-cell receptor (TCR) triggering and subsequent T-cell activation are essential for the adaptive immune response. Recently, multiple lines of evidence have shown that force transduction across the TCR complex is involved during TCR triggering, and that the T cell might use its force-generation machinery to probe the mechanical properties of the opposing antigen-presenting cell, giving rise to different signaling and physiological responses. Mechanistically, actin polymerization and turnover have been shown to be essential for force generation by T cells, but how these actin dynamics are regulated spatiotemporally remains poorly understood. Here, we report that traction forces generated by T cells are regulated by dynamic microtubules (MTs) at the interface. These MTs suppress Rho activation, nonmuscle myosin II bipolar filament assembly, and actin retrograde flow at the T-cell-substrate interface. Our results suggest a novel role of the MT cytoskeleton in regulating force generation during T-cell activation.T lymphocytes, central players in the adaptive immune response, are activated when T-cell receptors (TCRs) on their surface recognize cognate peptide-major histocompatibility complex (pMHC) expressed on the surface of antigen-presenting cells (APCs). A burst of actin polymerization is triggered upon TCR stimulation (1), leading to an enhancement of the cell/APC contact area as the T cell spreads over the surface of the APC (2) and the formation of a macromolecular protein assembly known as the immunological synapse (IS) (3, 4). Accompanying IS formation, T cells also undergo a rapid polarization of the microtubule (MT) cytoskeleton, within 1-2 min after initial contact, that facilitates directional secretion of cytokines and cytolytic factors toward the APC (5-7). Therefore, the contact zone between T cells and APCs is a site at which the MT and actin cytoskeletons could potentially interact to regulate signaling.Recent studies have established that T cells generate significant traction stresses at the cell-cell interface, albeit relatively weak compared with adherent cells (8-11). These forces, which peak 5-10 min after stimulation, facilitate T-cell activation, in part, by inducing conformational changes in the TCR-CD3 complex (12-15). Although actin polymerization/depolymerization dynamics are essential for T cells to maintain dynamic traction stresses and to drive calcium influx and integrin affinity maturation (9, 16, 17), the regulatory pathways that control these cytoskeletal forces are not completely understood. In particular, whether and how the polarized MT cytoskeleton interacts with the actin cytoskeleton and regulates force generation at the T-cell-APC contact remain open questions.MTs in the cell exist in two populations: dynamic/tyrosinated MTs and stable MTs that have undergone posttranslational modifications, including detyrosination and acetylation (18). Previous studies of T-cell activation have elucidated that microtubuleorganizing center (MTOC) translocation is associated with the formati...

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“…Rizvi, et al [26] recorded high mortality on Indian mustard followed by yellow sarson, gobhi sarson and cauliflower in all life stages of P. brassicae due to difference in nutritional values of host plants. The maximum survival fractions were recorded at later stage of development on cabbage as compared to other cole crops [27].…”

Section: Discussionmentioning

confidence: 99%

Stage Specific Life Table of Invasive Pest Mealybug, Phenacoccus Solenopsis (Tinsley) Under Cotton Field Conditions

Sahito

Kousar

Mangrio

et al. 2017

Current Research in Agricultural Sciences

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Article HistoryThe field study was conducted on at the experimental field of SALU -Khairpur during, 2016. Two hundred eggs were kept for each replication on cotton plants grown in large pots. When eggs hatched, the life table parameters such as; apparent mortality, survival fraction, mortality survivor ratio, indispensable mortality and k-value were studied. Natural enemies such as; Chrysoperla carneae, lady bird beetles, Spiders and Anasius bambawallae were found active on the potted and surrounding cotton plants in the field conditions. The total mortality in egg stage went to 19.00%. The mortality percentages of 1 st instars due to natural enemies recorded was (18.73%) while, in 2 nd instars (13.13%) mortality was recorded. The total combined mortality in 1 st and 2 nd instars was recorded (26.34%) and (15.64%), respectively. However, the mortality of 3 rd instars and pupae due to parasitoids were recorded (7.28%) with the total mortality (10.26%) and the total mortality (54.83%) in cotton potted plants was recorded. Consequently, (45.17%) of adults survived with male and female ratio as ♂1:6.52♀, respectively. The highest apparent mortality was (26.34%), indispensable mortality (96.89) and k-value (0.13) recorded in 1 st instar. The maximum survival fraction was recorded (0.90) in third instars/pupae with the total k-value generations (0.35). The study revealed that the predators and parasitoids should be encouraged in cotton field when mealybugs appear, because predators are highly voracious feeder of 1 st and 2 nd instars whereas; the parasitoid, A. bambawallae is known as main controlling natural enemy of cotton mealybug.Contribution/ Originality: This study documents over the biological parameters of cotton mealybug to check its, egg laying, mortality, survivor ratio, total life span, fecundity, fertility, different life stages, predators activity and aboitic factors with the different equations about this vigorous pest under cotton field conditions.

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Identification and Characterization of a Small Molecule Inhibitor of Formin-Mediated Actin Assembly

Cited by 342 publications

References 50 publications

The Mos-MAPK pathway regulates Diaphanous-related formin activity to drive cleavage furrow closure during polar body emission in starfish oocytes

The Mos-MAPK pathway regulates Diaphanous-related formin activity to drive cleavage furrow closure during polar body emission in starfish oocytes

Dynamic microtubules regulate cellular contractility during T-cell activation

Stage Specific Life Table of Invasive Pest Mealybug, Phenacoccus Solenopsis (Tinsley) Under Cotton Field Conditions

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