273 research outputs found
CO and C_2 Absorption Toward W40 IRS 1a
The H II region W40 harbors a small group of young, hot stars behind roughly
9 magnitudes of visual extinction. We have detected gaseous carbon monoxide
(CO) and diatomic carbon (C_2) in absorption toward the star W40 IRS 1a. The
2-0 R0, R1, and R2 lines of 12CO at 2.3 micron were measured using the CSHELL
on the NASA IR Telescope Facility (with upper limits placed on R3, R4, and R5)
yielding an N_CO of (1.1 +/- 0.2) x 10^18 cm^-2. Excitation analysis indicates
T_kin > 7 K. The Phillips system of C_2 transitions near 8775 Ang. was measured
using the Kitt Peak 4-m telescope and echelle spectrometer. Radiative pumping
models indicate a total C_2 column density of (7.0 +/- 0.4) x 10^14 cm^-2, two
excitation temperatures (39 and 126 K), and a total gas density of n ~ 250
cm^-3. The CO ice band at 4.7 micron was not detected, placing an upper limit
on the CO depletion of delta < 1 %. We postulate that the sightline has
multiple translucent components and is associated with the W40 molecular cloud.
Our data for W40 IRS 1a, coupled with other sightlines, shows that the ratio of
CO/C_2 increases from diffuse through translucent environs. Finally, we show
that the hydrogen to dust ratio seems to remain constant from diffuse to dense
environments, while the CO to dust ratio apparently does not.Comment: To appear in The Astrophysical Journal 17 pages total, 5 figures Also
available at http://casa.colorado.edu/~shuping/research/w40/w40.htm
Adenovirus Recruits Dynein by an Evolutionary Novel Mechanism Involving Direct Binding to pH-Primed Hexon
Following receptor-mediated uptake into endocytic vesicles and escape from the endosome, adenovirus is transported by cytoplasmic dynein along microtubules to the perinuclear region of the cell. How motor proteins are recruited to viruses for their own use has begun to be investigated only recently. We review here the evidence for a role for dynein and other motor proteins in adenovirus infectivity. We also discuss the implications of recent studies on the mechanism of dynein recruitment to adenovirus for understanding the relationship between pathogenic and physiological cargo recruitment and for the evolutionary origins of dynein-mediated adenovirus transport
Neuronal migration defects in the Loa dynein mutant mouse
<p>Abstract</p> <p>Background</p> <p>Cytoplasmic dynein and its regulatory proteins have been implicated in neuronal and non-neuronal cell migration. A genetic model for analyzing the role of cytoplasmic dynein specifically in these processes has, however, been lacking. The Loa (Legs at odd angles) mouse with a mutation in the dynein heavy chain has been the focus of an increasing number of studies for its role in neuron degeneration. Despite the location of this mutation in the tail domain of the dynein heavy chain, we previously found a striking effect on coordination between the two dynein motor domains, resulting in a defect in dynein run length <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>We have now tested for effects of the Loa mutation on neuronal migration in the developing neocortex. Loa homozygotes showed clear defects in neocortical lamination and neuronal migration resulting from a reduction in the rate of radial migration of bipolar neurons.</p> <p>Conclusions</p> <p>These results present a new genetic model for understanding the dynein pathway and its functions during neuronal migration. They also provide the first evidence for a link between dynein processivity and somal movement, which is essential for proper development of the brain.</p
NudE and NudEL are required for mitotic progression and are involved in dynein recruitment to kinetochores
NudE and NudEL are related proteins that interact with cytoplasmic dynein and LIS1. Their functional relationship and involvement in LIS1 and dynein regulation are not completely understood. We find that NudE and NudEL each localize to mitotic kinetochores before dynein, dynactin, ZW10, and LIS1 and exhibit additional temporal and spatial differences in distribution from the motor protein. Inhibition of NudE and NudEL caused metaphase arrest with misoriented chromosomes and defective microtubule attachment. Dynein and dynactin were both displaced from kinetochores by the injection of an anti-NudE/NudEL antibody. Dynein but not dynactin interacted with NudE surprisingly through the dynein intermediate and light chains but not the motor domain. Together, these results identify a common function for NudE and NudEL in mitotic progression and identify an alternative mechanism for dynein recruitment to and regulation at kinetochores
Direct Interaction of Pericentrin with Cytoplasmic Dynein Light Intermediate Chain Contributes to Mitotic Spindle Organization
Pericentrin is a conserved protein of the centrosome involved in microtubule organization. To better understand pericentrin function, we overexpressed the protein in somatic cells and assayed for changes in the composition and function of mitotic spindles and spindle poles. Spindles in pericentrin-overexpressing cells were disorganized and mispositioned, and chromosomes were misaligned and missegregated during cell division, giving rise to aneuploid cells. We unexpectedly found that levels of the molecular motor cytoplasmic dynein were dramatically reduced at spindle poles. Cytoplasmic dynein was diminished at kinetochores also, and the dynein-mediated organization of the Golgi complex was disrupted. Dynein coimmunoprecipitated with overexpressed pericentrin, suggesting that the motor was sequestered in the cytoplasm and was prevented from associating with its cellular targets. Immunoprecipitation of endogenous pericentrin also pulled down cytoplasmic dynein in untransfected cells. To define the basis for this interaction, pericentrin was coexpressed with cytoplasmic dynein heavy (DHCs), intermediate (DICs), and light intermediate (LICs) chains, and the dynamitin and p150Glued subunits of dynactin. Only the LICs coimmunoprecipitated with pericentrin. These results provide the first physiological role for LIC, and they suggest that a pericentrin–dynein interaction in vivo contributes to the assembly, organization, and function of centrosomes and mitotic spindles
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Role of kinesins in directed adenovirus transport and cytoplasmic exploration
Many viruses, including adenovirus, exhibit bidirectional transport along microtubules following cell entry. Cytoplasmic dynein is responsible for microtubule minus end transport of adenovirus capsids after endosomal escape. However, the identity and roles of the opposing plus end-directed motor(s) remain unknown. We performed an RNAi screen of 38 kinesins, which implicated Kif5B (kinesin-1 family) and additional minor kinesins in adenovirus 5 (Ad5) capsid translocation. Kif5B RNAi markedly increased centrosome accumulation of incoming Ad5 capsids in human A549 pulmonary epithelial cells within the first 30 min post infection, an effect dramatically enhanced by blocking Ad5 nuclear pore targeting using leptomycin B. The Kif5B RNAi phenotype was rescued by expression of RNAi-resistant Kif5A, B, or C, and Kif4A. Kif5B RNAi also inhibited a novel form of microtubule-based “assisted-diffusion” behavior which was apparent between 30 and 60 min p.i. We found the major capsid protein penton base (PB) to recruit kinesin-1, distinct from the hexon role we previously identified for cytoplasmic dynein binding. We propose that adenovirus uses independently recruited kinesin and dynein for directed transport and for a more random microtubule-based assisted diffusion behavior to fully explore the cytoplasm before docking at the nucleus, a mechanism of potential importance for physiological cargoes as well
Severe NDE1-mediated microcephaly results from neural progenitor cell cycle arrests at multiple specific stages
Microcephaly is a cortical malformation disorder characterized by an abnormally small brain. Recent studies have revealed severe cases of microcephaly resulting from human mutations in the NDE1 gene, which is involved in the regulation of cytoplasmic dynein. Here using in utero electroporation of NDE1 short hairpin RNA (shRNA) in embryonic rat brains, we observe cell cycle arrest of proliferating neural progenitors at three distinct stages: during apical interkinetic nuclear migration, at the G2-to-M transition and in regulation of primary cilia at the G1-to-S transition. RNAi against the NDE1 paralogue NDEL1 has no such effects. However, NDEL1 overexpression can functionally compensate for NDE1, except at the G2-to-M transition, revealing a unique NDE1 role. In contrast, NDE1 and NDEL1 RNAi have comparable effects on postmitotic neuronal migration. These results reveal that the severity of NDE1-associated microcephaly results not from defects in mitosis, but rather the inability of neural progenitors to ever reach this stage
LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages
Mutations in the human LIS1 gene cause the smooth brain disease classical lissencephaly. To understand the underlying mechanisms, we conducted in situ live cell imaging analysis of LIS1 function throughout the entire radial migration pathway. In utero electroporation of LIS1 small interference RNA and short hairpin dominant negative LIS1 and dynactin cDNAs caused a dramatic accumulation of multipolar progenitor cells within the subventricular zone of embryonic rat brains. This effect resulted from a complete failure in progression from the multipolar to the migratory bipolar state, as revealed by time-lapse analysis of brain slices. Surprisingly, interkinetic nuclear oscillations in the radial glial progenitors were also abolished, as were cell divisions at the ventricular surface. Those few bipolar cells that reached the intermediate zone also exhibited a complete block in somal translocation, although, remarkably, process extension persisted. Finally, axonal growth also ceased. These results identify multiple distinct and novel roles for LIS1 in nucleokinesis and process dynamics and suggest that nuclear position controls neural progenitor cell division
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