Interaction of Aurora-A and centrosomin at the microtubule-nucleating site in Drosophila and mammalian cells

A mitosis-specific Aurora-A kinase has been implicated in microtubule organization and spindle assembly in diverse organisms. However, exactly how Aurora-A controls the microtubule nucleation onto centrosomes is unknown. Here, we show that Aurora-A specifically binds to the COOH-terminal domain of a Drosophila centrosomal protein, centrosomin (CNN), which has been shown to be important for assembly of mitotic spindles and spindle poles. Aurora-A and CNN are mutually dependent for localization at spindle poles, which is required for proper targeting of γ-tubulin and other centrosomal components to the centrosome. The NH2-terminal half of CNN interacts with γ-tubulin, and induces cytoplasmic foci that can initiate microtubule nucleation in vivo and in vitro in both Drosophila and mammalian cells. These results suggest that Aurora-A regulates centrosome assembly by controlling the CNN's ability to targeting and/or anchoring γ-tubulin to the centrosome and organizing microtubule-nucleating sites via its interaction with the COOH-terminal sequence of CNN

イネ腋芽の成長評価用４次元MRIマイクロスコピーの開発

科学研究費助成事業 研究成果報告書：基盤研究(C)2015-2017課題番号 : 15K0471

CHO1, a mammalian kinesin-like protein, interacts with F-actin and is involved in the terminal phase of cytokinesis

CHO1 is a kinesin-like protein of the mitotic kinesin-like protein (MKLP)1 subfamily present in central spindles and midbodies in mammalian cells. It is different from other subfamily members in that it contains an extra ∼300 bp in the COOH-terminal tail. Analysis of the chicken genomic sequence showed that heterogeneity is derived from alternative splicing, and exon 18 is expressed in only the CHO1 isoform. CHO1 and its truncated isoform MKLP1 are coexpressed in a single cell. Surprisingly, the sequence encoded by exon 18 possesses a capability to interact with F-actin, suggesting that CHO1 can associate with both microtubule and actin cytoskeletons. Microinjection of exon 18–specific antibodies did not result in any inhibitory effects on karyokinesis and early stages of cytokinesis. However, almost completely separated daughter cells became reunited to form a binulceate cell, suggesting that the exon 18 protein may not have a role in the formation and ingression of the contractile ring in the cortex. Rather, it might be involved directly or indirectly in the membrane events necessary for completion of the terminal phase of cytokinesis

Molecular Adsorption Behavior on an Au(111) Surface(STM-other surfaces)

Scanning tunneling microscopy (STM) was used to study molecular adsorption behavior on reconstructed Au(111) surface. The STM images of ethyl 4-[2-(2-pyrazyl)ethenyl]cinnamate (E25PC) molecules adsorbed on Au(111) revealed ordered nucleation of molecular islands at the initial growth stage. The islands grew with spacing 38 Å in rows 77 Å apart. The periodicity of 38 Å×77 Å corresponds to that of STM images of bare Au(111) reconstructed surface in air. The behavior of molecules adsorbed on Au(111) is discussed from a view point of Au(111) herringbone reconstruction

Oval gradient coils for an open magnetic resonance imaging system with a vertical magnetic field

Existing open magnetic resonance imaging (MRI) systems use biplanar gradient coils for the spatial encoding of signals. We propose using novel oval gradient coils for an open vertical-field MRI. We designed oval gradients for a 0.3 T open MRI system and showed that such a system could outperform a traditional biplanar gradient system while maintaining adequate gradient homogeneity and subject accessibility. Such oval gradient coils would exhibit high efficiency, low inductance and resistance, and high switching capability. Although the designed oval Y and Z coils showed more heat dissipation and less cooling capability than biplanar coils with the same gap, they showed an efficient heat-dissipation path to the surrounding air, which would alleviate the heat problem. The performance of the designed oval-coil system was demonstrated experimentally by imaging a human hand

A RUNX-targeted gene switch-off approach modulates the BIRC5/PIF1-p21 pathway and reduces glioblastoma growth in mice

Glioblastoma is the most common adult brain tumour, representing a high degree of malignancy. Transcription factors such as RUNX1 are believed to be involved in the malignancy of glioblastoma. RUNX1 functions as an oncogene or tumour suppressor gene with diverse target genes. Details of the effects of RUNX1 on the acquisition of malignancy in glioblastoma remain unclear. Here, we show that RUNX1 downregulates p21 by enhancing expressions of BIRC5 and PIF1, conferring anti-apoptotic properties on glioblastoma. A gene switch-off therapy using alkylating agent-conjugated pyrrole-imidazole polyamides, designed to fit the RUNX1 DNA groove, decreased expression levels of BIRC5 and PIF1 and induced apoptosis and cell cycle arrest via p21. The RUNX1-BIRC5/PIF1-p21 pathway appears to reflect refractory characteristics of glioblastoma and thus holds promise as a therapeutic target. RUNX gene switch-off therapy may represent a novel treatment for glioblastoma

The Circulatory Risk in Communities Study (CIRCS): A Long-Term Epidemiological Study for Lifestyle-Related Disease Among Japanese Men and Women Living in Communities

The Circulatory Risk in Communities Study (CIRCS) is an ongoing community-based epidemiological study of lifestyle-related disease involving dynamic prospective cohorts of approximately 12,000 adults from five communities of Japan: Ikawa, Ishizawa and Kita-Utetsu (Akita Prefecture), Minami-Takayasu (Osaka Prefecture), Noichi (Kochi Prefecture), and Kyowa (Ibaraki Prefecture). One of the most notable features of CIRCS is that it is not only an observational cohort study to identify risk factors for cardiovascular diseases (CVD), such as stroke, coronary heart disease, and sudden cardiac death, but it also involves prevention programs for CVD. Using basic, clinical, epidemiological, and statistical techniques, CIRCS has clarified characteristics of CVD and the related risk factors to develop specific methodologies towards CVD prevention in Japanese middle-aged or older adults for more than half a century

Human Immunodeficiency Virus Type 1 Vpr Induces G(2) Checkpoint Activation by Interacting with the Splicing Factor SAP145

Vpr, the viral protein R of human immunodeficiency virus type 1, induces G(2) cell cycle arrest and apoptosis in mammalian cells via ATR (for “ataxia-telangiectasia-mediated and Rad3-related”) checkpoint activation. The expression of Vpr induces the formation of the γ-histone 2A variant X (H2AX) and breast cancer susceptibility protein 1 (BRCA1) nuclear foci, and a C-terminal domain is required for Vpr-induced ATR activation and its nuclear localization. However, the cellular target of Vpr, as well as the mechanism of G(2) checkpoint activation, was unknown. Here we report that Vpr induces checkpoint activation and G(2) arrest by binding to the CUS1 domain of SAP145 and interfering with the functions of the SAP145 and SAP49 proteins, two subunits of the multimeric splicing factor 3b (SF3b). Vpr interacts with and colocalizes with SAP145 through its C-terminal domain in a speckled distribution. The depletion of either SAP145 or SAP49 leads to checkpoint-mediated G(2) cell cycle arrest through the induction of nuclear foci containing γ-H2AX and BRCA1. In addition, the expression of Vpr excludes SAP49 from the nuclear speckles and inhibits the formation of the SAP145-SAP49 complex. To conclude, these results point out the unexpected roles of the SAP145-SAP49 splicing factors in cell cycle progression and suggest that cellular expression of Vpr induces checkpoint activation and G(2) arrest by interfering with the function of SAP145-SAP49 complex in host cells