Roles of motor proteins in building microtubule-based structures: a basic principle of cellular design

AbstractEukaryotic cells must build a complex infrastructure of microtubules (MTs) and associated proteins to carry out a variety of functions. A growing body of evidence indicates that a major function of MT-associated motor proteins is to assemble and maintain this infrastructure. In this context, we examine the mechanisms utilized by motors to construct the arrays of MTs and associated proteins contained within the mitotic spindle, neuronal processes, and ciliary axonemes. We focus on the capacity of motors to drive the ‘sliding filament mechanism’ that is involved in the construction and maintenance of spindles, axons and dendrites, and on a type of particle transport called ‘intraflagellar transport’ which contributes to the assembly and maintenance of axonemes

Mitosis, microtubules, and the matrix

The mechanical events of mitosis depend on the action of microtubules and mitotic motors, but whether these spindle components act alone or in concert with a spindle matrix is an important question

Three microtubule severing enzymes contribute to the “Pacman-flux” machinery that moves chromosomes

Chromosomes move toward mitotic spindle poles by a Pacman-flux mechanism linked to microtubule depolymerization: chromosomes actively depolymerize attached microtubule plus ends (Pacman) while being reeled in to spindle poles by the continual poleward flow of tubulin subunits driven by minus-end depolymerization (flux). We report that Pacman-flux in Drosophila melanogaster incorporates the activities of three different microtubule severing enzymes, Spastin, Fidgetin, and Katanin. Spastin and Fidgetin are utilized to stimulate microtubule minus-end depolymerization and flux. Both proteins concentrate at centrosomes, where they catalyze the turnover of γ-tubulin, consistent with the hypothesis that they exert their influence by releasing stabilizing γ-tubulin ring complexes from minus ends. In contrast, Katanin appears to function primarily on anaphase chromosomes, where it stimulates microtubule plus-end depolymerization and Pacman-based chromatid motility. Collectively, these findings reveal novel and significant roles for microtubule severing within the spindle and broaden our understanding of the molecular machinery used to move chromosomes

Drosophila EB1 is important for proper assembly, dynamics, and positioning of the mitotic spindle

EB1 is an evolutionarily conserved protein that localizes to the plus ends of growing microtubules. In yeast, the EB1 homologue (BIM1) has been shown to modulate microtubule dynamics and link microtubules to the cortex, but the functions of metazoan EB1 proteins remain unknown. Using a novel preparation of the Drosophila S2 cell line that promotes cell attachment and spreading, we visualized dynamics of single microtubules in real time and found that depletion of EB1 by RNA-mediated inhibition (RNAi) in interphase cells causes a dramatic increase in nondynamic microtubules (neither growing nor shrinking), but does not alter overall microtubule organization. In contrast, several defects in microtubule organization are observed in RNAi-treated mitotic cells, including a drastic reduction in astral microtubules, malformed mitotic spindles, defocused spindle poles, and mispositioning of spindles away from the cell center. Similar phenotypes were observed in mitotic spindles of Drosophila embryos that were microinjected with anti-EB1 antibodies. In addition, live cell imaging of mitosis in Drosophila embryos reveals defective spindle elongation and chromosomal segregation during anaphase after antibody injection. Our results reveal crucial roles for EB1 in mitosis, which we postulate involves its ability to promote the growth and interactions of microtubules within the central spindle and at the cell cortex

Spindle microtubules in flux

Accurate and timely chromosome segregation is a task performed within meiotic and mitotic cells by a specialized force-generating structure - the spindle. This micromachine is constructed from numerous proteins, most notably the filamentous microtubules that form a structural framework for the spindle and also transmit forces through it. Poleward flux is an evolutionarily conserved mechanism used by spindle microtubules both to move chromosomes and to regulate spindle length. Recent studies have identified a microtubule-depolymerizing kinesin as a key force-generating component required for flux. On the basis of these findings, we propose a new model for flux powered by a microtubule-disassembly mechanism positioned at the spindle pole. In addition, we use the flux model to explain the results of spindle manipulation experiments to illustrate the importance of flux for proper chromosome positioning

Shared etiology of psychotic experiences and depressive symptoms in adolescence: a longitudinal twin study

Psychotic disorders and major depression, both typically adult-onset conditions, often co-occur. At younger ages psychotic experiences and depressive symptoms are often reported in the community. We used a genetically sensitive longitudinal design to investigate the relationship between psychotic experiences and depressive symptoms in adolescence. A representative community sample of twins from England and Wales was employed. Self-rated depressive symptoms, paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia, and parent-rated negative symptoms were collected when the twins were age 16 (N = 9618) and again on a representative subsample 9 months later (N = 2873). Direction and aetiology of associations were assessed using genetically informative cross-lagged models. Depressive symptoms were moderately correlated with paranoia, hallucinations, and cognitive disorganization. Lower correlations were observed between depression and anhedonia, and depression and parent-rated negative symptoms. Nonsignificant correlations were observed between depression and grandiosity. Largely the same genetic effects influenced depression and paranoia, depression and hallucinations, and depression and cognitive disorganization. Modest overlap in environmental influences also played a role in the associations. Significant bi-directional longitudinal associations were observed between depression and paranoia. Hallucinations and cognitive disorganization during adolescence were found to impact later depression, even after controlling for earlier levels of depression. Our study shows that psychotic experiences and depression, as traits in the community, have a high genetic overlap in mid-adolescence. Future research should test the prediction stemming from our longitudinal results, namely that reducing or ameliorating positive and cognitive psychotic experiences in adolescence would decrease later depressive symptoms

The WiggleZ Dark Energy Survey: Star-formation in UV-luminous galaxies from their luminosity functions

We present the ultraviolet (UV) luminosity function of galaxies from the GALEX Medium Imaging Survey with measured spectroscopic redshifts from the first data release of the WiggleZ Dark Energy Survey. This sample selects galaxies with high star formation rates: at 0.6 < z < 0.9 the median star formation rate is at the upper 95th percentile of optically-selected (r<22.5) galaxies and the sample contains about 50 per cent of all NUV < 22.8, 0.6 < z < 0.9 starburst galaxies within the volume sampled. The most luminous galaxies in our sample (-21.0>M_NUV>-22.5) evolve very rapidly with a number density declining as (1+z)^{5\pm 1} from redshift z = 0.9 to z = 0.6. These starburst galaxies (M_NUV<-21 is approximately a star formation rate of 30 \msuny) contribute about 1 per cent of cosmic star formation over the redshift range z=0.6 to z=0.9. The star formation rate density of these very luminous galaxies evolves rapidly, as (1+z)^{4\pm 1}. Such a rapid evolution implies the majority of star formation in these large galaxies must have occurred before z = 0.9. We measure the UV luminosity function in 0.05 redshift intervals spanning 0.1<z<0.9, and provide analytic fits to the results. At all redshifts greater than z=0.55 we find that the bright end of the luminosity function is not well described by a pure Schechter function due to an excess of very luminous (M_NUV<-22) galaxies. These luminosity functions can be used to create a radial selection function for the WiggleZ survey or test models of galaxy formation and evolution. Here we test the AGN feedback model in Scannapieco et al. (2005), and find that this AGN feedback model requires AGN feedback efficiency to vary with one or more of the following: stellar mass, star formation rate and redshift.Comment: 27 pages; 13 pages without appendices. 22 figures; 11 figures in the main tex

Photorefractive self-focusing and defocusing as an optical limiter

Focusing and defocusing of laser light has been observed for many years. Kerr type materials exhibit this effect but only for high intensities. We show experimental evidence that photorefractive materials can also produce dramatic focusing and defocusing. Whereas Kerr materials produce this effect for high intensities, photorefractive materials produce these effects independent of intensity indicating that this effect would be ideal for an optical limiter. We compare the characteristics of Kerr and photorefractive materials, discuss the physical models for both materials and present experimental evidence for photorefractive defocusing. Self-focusing and defocusing was observed for any incident polarization although the effect was more pronounced using extraordinary polarized light. In addition, self-focusing or defocusing could be observed depending on the direction of the applied electric field. When the applied field was in the same direction as the crystal spontaneous polarization, focusing was observed. When the applied field was opposite the material spontaneous polarization, the incident laser light was dramatically defocused

The WiggleZ Dark Energy Survey: improved distance measurements to z = 1 with reconstruction of the baryonic acoustic feature

We present significant improvements in cosmic distance measurements from the WiggleZ Dark Energy Survey, achieved by applying the reconstruction of the baryonic acoustic feature technique. We show using both data and simulations that the reconstruction technique can often be effective despite patchiness of the survey, significant edge effects and shot-noise. We investigate three redshift bins in the redshift range 0.2 < z < 1, and in all three find improvement after reconstruction in the detection of the baryonic acoustic feature and its usage as a standard ruler. We measure model-independent distance measures DV(rsfid/rs) of 1716 ± 83, 2221 ± 101, 2516 ± 86 Mpc (68 per cent CL) at effective redshifts z = 0.44, 0.6, 0.73, respectively, where DV is the volume-averaged distance, and rs is the sound horizon at the end of the baryon drag epoch. These significantly improved 4.8, 4.5 and 3.4 per cent accuracy measurements are equivalent to those expected from surveys with up to 2.5 times the volume of WiggleZ without reconstruction applied. These measurements are fully consistent with cosmologies allowed by the analyses of the Planck Collaboration and the Sloan Digital Sky Survey. We provide the DV(rsfid/rs) posterior probability distributions and their covariances. When combining these measurements with temperature fluctuations measurements of Planck, the polarization of Wilkinson Microwave Anisotropy Probe 9, and the 6dF Galaxy Survey baryonic acoustic feature, we do not detect deviations from a flat Λ cold dark matter (ΛCDM) model. Assuming this model, we constrain the current expansion rate to H₀ = 67.15 ± 0.98 km s⁻¹Mpc⁻¹. Allowing the equation of state of dark energy to vary, we obtain wDE = −1.080 ± 0.135. When assuming a curved ΛCDM model we obtain a curvature value of ΩK = −0.0043 ± 0.0047