Cdk1-dependent phosphoinhibition of a formin-F-BAR interaction opposes cytokinetic contractile ring formation

© 2018 Willet et al. In Schizosaccharomyces pombe, cytokinesis requires the assembly and constriction of an actomyosin-based contractile ring (CR). A single essential formin, Cdc12, localizes to the cell middle upon mitotic onset and nucleates the F-actin of the CR. Cdc12 medial recruitment is mediated in part by its direct binding to the F-BAR scaffold Cdc15. Given that Cdc12 is hyperphosphorylated in M phase, we explored whether Cdc12 phosphoregulation impacts its association with Cdc15 during mitosis. We found that Cdk1, a major mitotic kinase, phosphorylates Cdc12 on six N-terminal residues near the Cdc15-binding site, and phosphorylation on these sites inhibits its interaction with the Cdc15 F-BAR domain. Consistent with this finding, a cdc12 mutant with all six Cdk1 sites changed to phosphomimetic residues (cdc12-6D) displays phenotypes similar to cdc12-P31A, in which the Cdc15-binding motif is disrupted; both show reduced Cdc12 at the CR and delayed CR formation. Together, these results indicate that Cdk1 phosphorylation of formin Cdc12 antagonizes its interaction with Cdc15 and thereby opposes Cdc12\u27s CR localization. These results are consistent with a general role of Cdk1 in inhibiting cytokinesis until chromosome segregation is complete

Formin-based control of the actin cytoskeleton during cytokinesis

Cytokinesis, the terminal event in the canonical cell cycle, physically separates daughter cells following mitosis. For cleavage to occur in many eukaryotes, a cytokinetic ring must assemble and constrict between divided genomes. Although dozens of different molecules localize to and participate within the cytokinetic ring, the core machinery comprises linear actin filaments. Accordingly, formins, which nucleate and elongate F-actin (filamentous actin) for the cytokinetic ring, are required for cytokinesis in diverse species. In the present article, we discuss specific modes of formin-based actin regulation during cell division and highlight emerging mechanisms and questions on this topic. © 2013 Biochemical Society

Educating Social Scholars: Examining Novice Researchers’ Practices with Social Media

Recent articles in the educational research fi eld have called for a stronger research focus on students’ learning with everyday technologies in-and-out-of classrooms and on the changing nature of scholars’ practices in light of technological advancements. We present fi ndings from a mixed methods study of whether and how novice researchers understand and practice social scholarship – a concept currently being debated in various disciplines – which seeks to leverage social media affordances to create expanded sites for research collaboration, peer review, dissemination, and evaluation of research impact. We found that novice researchers focused almost exclusively on social scholarship of discovery and much less on interdisciplinary, teaching, or applied scholarship. Insights from this study will appeal to those interested in examining the theory and design of graduate student learning and faculty development

Theory of Shubnikov--De Haas Oscillations Around the ν=1/2\nu=1/2 Filling Factor of the Landau Level: Effect of Gauge Field Fluctuations

We present a theory of magnetooscillations around the $\nu =1/2$ Landau level filling factor based on a model with a fluctuating Chern--Simons field. The quasiclassical treatment of the problem is appropriate and leads to an unconventional $\exp\left[-(\pi/\omega_c\tau^*_{1/2})^4\right]$ behavior of the amplitude of oscillations. This result is in good qualitative agreement with available experimental data.Comment: Revtex, 4 pages, 1 figure attached as PostScript fil

Instantons and the spectral function of electrons in the half-filled Landau level

We calculate the instanton-anti-instanton action $S_{M {\bar M}} (\tau)$ in the gauge theory of the half-filled Landau level. It is found that $S_{M {\bar M}} (\tau) = (3 - \eta) \left [ \Omega_0 (\eta) \ \tau \right ]^{1 / (3 - \eta)}$ for a class of interactions $v ({\bf q}) = V_0 / q^{\eta} \ ( 0 \leq \eta < 2 )$ between electrons. This means that the instanton-anti-instanton pairs are confining so that a well defined `charged' composite fermion can exist. It is also shown that $S_{M {\bar M}} (\tau)$ can be used to calculate the spectral function of electrons from the microscopic theory within a semiclassical approximation. The resulting spectral function varies as $e^{ - \left [ \Omega_0 (\eta) / \omega \right ]^{1 / ( 2 - \eta ) } }$ at low energies.Comment: 13 pages, Plain Tex, MIT-CMT-APR-9

Specific heat and validity of quasiparticle approximation in the half-filled Landau level

We calculate the specific heat of composite fermion system in the half-filled Landau level. Two different methods are used to examine validity of the quasiparticle approximation when the two-body interaction is given by $V(q) = V_0 / q^{2-\eta}$ ($1 \le \eta \le 2$). The singular part of the specific heat is calculated from the free energy of the gauge field, which is compared with the specific heat calculated from the quasiparticle approximation via the singular self-energy correction due to the gauge field fluctuations. It turns out that two results are in general different and they coincide only for the case of the Coulomb interaction ($\eta = 1$). This result supports the fact that the quasiparticle approximation is valid only for the case of the Coulomb interaction. It is emphasized that this result is obtained by looking at a gauge-invariant quantity -- the specific heat.Comment: 8 pages, Revte

The Haldane-Rezayi Quantum Hall State and Magnetic Flux

We consider the general abelian background configurations for the Haldane-Rezayi quantum Hall state. We determine the stable configurations to be the ones with the spontaneous flux of $(\Z+1/2) \phi_0$ with $\phi_0 = hc/e$. This gives the physical mechanism by which the edge theory of the state becomes identical to the one for the 331 state. It also provides a new experimental consequence which can be tested in the enigmatic $\nu=5/2$ plateau in a single layer system.Comment: RevTex, 5 pages, 2 figures. v2:minor corrections. v4: published version. Discussion on the thermodynamic limit adde

SIN-dependent phosphoinhibition of formin multimerization controls fission yeast cytokinesis

Many eukaryotes accomplish cell division by building and constricting a medial actomyosin-based cytokinetic ring (CR). In Schizosaccharomyces pombe, a Hippo-related signaling pathway termed the septation initiation network (SIN) controls CR formation, maintenance, and constriction. However, how the SIN regulates integral CR components was unknown. Here, we identify the essential cytokinetic formin Cdc12 as a key CR substrate of SIN kinase Sid2. Eliminating Sid2-mediated Cdc12 phosphorylation leads to persistent Cdc12 clustering, which prevents CR assembly in the absence of anillin-like Mid1 and causes CRs to collapse when cytokinesis is delayed. Molecularly, Sid2 phosphorylation of Cdc12 abrogates multimerization of a previously unrecognized Cdc12 domain that confers F-actin bundling activity. Taken together, our findings identify a SIN-triggered oligomeric switch that modulates cytokinetic formin function, revealing a novel mechanism of actin cytoskeleton regulation during cell division. © 2013 Bohnert et al

Comparative Effects of University of Wisconsin and Euro-Collins Solutions on Pulmonary Mitochondrial Function after Ischemia and Reperfusion

peer reviewedBACKGROUND: The aim of this study was to compare the effects of Euro-Collins and University of Wisconsin solutions on pulmonary mitochondrial function after cold ischemia and subsequent warm reperfusion. METHODS: Seventeen pigs underwent lung harvesting after classical lung flush with either University of Wisconsin or Euro-Collins solutions. The mitochondria were isolated from fresh swine lungs, from swine lungs subjected to 24 hr of cold ischemia, and from swine lungs subjected to 24 hr of ischemia followed by 30 min of subsequent ex vivo reperfusion at 37 degrees C with Krebs-Henseleit buffer solution and air ventilation. Mitochondrial oxidative phosphorylation parameters were determined in isolated mitochondria by in vitro measurement of oxygen consumption rates. During reperfusion, the lung function was assessed by the pulmonary aerodynamic parameters and the pulmonary vascular resistance. RESULTS: Relative to controls, mitochondria submitted to cold ischemia showed an alteration in the oxidoreductase activities of the respiratory chain. However, the yield of oxidative phosphorylation was conserved. After reperfusion, pulmonary mitochondria underwent a significant worsening in the oxidoreductase activities of the respiratory chain, and a decrease in the respiratory control and the efficiency of oxidative phosphorylation. Meanwhile, the reperfused lungs showed evidence of early dysfunction, assessed by the aerodynamic parameters and pulmonary vascular resistance. In this model, there was no advantage of University of Wisconsin solution over Euro-Collins solution. CONCLUSIONS: The mild mitochondrial alterations after cold ischemia were not sufficient to explain the limited tolerance of lung to ischemia. After reperfusion, the mitochondrial damage was more severe and could be involved in the posttransplant lung dysfunction

Stability of the compressible quantum Hall state around the half-filled Landau level

We study the compressible states in the quantum Hall system using a mean field theory on the von Neumann lattice. In the lowest Landau level, a kinetic energy is generated dynamically from Coulomb interaction. The compressibility of the state is calculated as a function of the filling factor $\nu$ and the width $d$ of the spacer between the charge carrier layer and dopants. The compressibility becomes negative below a critical value of $d$ and the state becomes unstable at $\nu=1/2$. Within a finite range around $\nu=1/2$, the stable compressible state exists above the critical value of $d$.Comment: 4 pages, 4 Postscript figures, RevTe