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Genes to Cells: Devoted to Molecular & Cellular Mechanisms

Hitoshi Inada, Keiko Numayama-Tsuruta, Kentaro Mochizuki, Makiko Sasaki-Hoshino, Noriko Osumi
Fabp7 gene encodes a brain-specific fatty acid-binding protein that is widely used as a marker for neural stem cells. Here, we report that the activity of rat Fabp7 promoter was regulated directly by a transcription factor, Pax6. Deletion analyses identified an essential region (-837 to -64 from transcription start site) in the rat Fabp7 promoter. This region controls promoter activity in rat embryos and in the mouse cultured cell line MEB5. Over-expressing wild-type Pax6 or a dominant-negative Pax6 mutant enhanced and suppressed, respectively, the promoter activity...
July 9, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Mitsuhide Noshiro, Takeshi Kawamoto, Ayumu Nakashima, Noritsugu Ozaki, Toshinori Ueno, Masayumi Saeki, Kiyomasa Honda, Katsumi Fujimoto, Yukio Kato
Obesity is a major public health problem in developed countries resulting from increased food intake and decreased energy consumption and usually associated with abnormal lipid metabolism. Here, we show that DEC1, a basic helix-loop-helix transcription factor, plays an important role in the regulation of lipid consumption in mouse brown adipose tissue (BAT), which is the major site of thermogenesis. Homozygous Dec1 deletion attenuated high-fat-diet-induced obesity, adipocyte hypertrophy, fat volume and hepatic steatosis...
July 3, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Keita Masuko, Hirofumi Furuhashi, Kanae Komaba, Eriko Numao, Rumi Nakajima, Naoyuki Fuse, Shoichiro Kurata
Drosophila imaginal discs often change their cell fate under stress conditions, and this phenomenon, called transdetermination (TD), has long been a useful model for studying cell fate plasticity during regeneration. We previously identified a chromatin-associated protein, Winged Eye (Wge), which induces eye-to-wing TD upon its over-expression in eye imaginal discs. However, the molecular mechanism of Wge-mediated TD remains obscure. Here, we analyzed Wge-interacting proteins and found that several heterochromatin-related proteins, including a nuclear lamina protein, Lamin (Lam), were associated with Wge protein in cultured cells...
July 2, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Rie Kokuda, Risayo Watanabe, Daisuke Okuzaki, Hiroki Akamatsu, Chitose Oneyama
The tyrosine kinase c-Src is frequently overexpressed and activated in a wide variety of human cancers. However, the molecular mechanisms responsible for the upregulation of c-Src remain elusive. To examine whether microRNA-mediated c-Src upregulation promotes cancer progression, we screened miRNAs with complementarity to the 3'-UTR of c-Src mRNA. Among these miRNAs, down-regulation of miR-137 was tightly associated with c-Src-mediated tumor progression of human colon cancer cells/tissues. Re-expression of miR-137 in human colon cancer cells suppressed tumor growth and caused the disruption of focal contacts, suppression of cell adhesion, and invasion, although restoration of c-Src in miR-137-treated cells could not fully rescue the tumor-suppressive effect of miR-137...
July 2, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Hoa Q Pham, Kazuaki Yoshioka, Hiromi Mohri, Hiroki Nakata, Sho Aki, Kazuhiro Ishimaru, Noriko Takuwa, Yoh Takuwa
Phosphatidylinositol 3-phosphate (PI(3)P) is the predominant phosphoinositide species in early endosomes and autophagosomes, in which PI(3)P dictates traffic of these organelles. Phosphoinositide levels are tightly regulated by lipid-kinases and -phosphatases; however, a phosphatase that converts PI(3)P back to phosphatidylinositol in the endosomal and autophagosomal compartments is not fully understood. We investigated the subcellular distribution and functions of myotubularin-related protein-4 (MTMR4), which is distinct among other MTMRs in that it possesses a PI(3)P-binding FYVE domain, in lung alveolar epithelium-derived A549 cells...
July 2, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Momoko Kobayashi, Kaya Watanabe, Ritsuko Matsumura, Nozomi Anayama, Akio Miyamoto, Hitoshi Miyazaki, Koyomi Miyazaki, Takashi Shimizu, Makoto Akashi
Circadian dysfunction perturbs the female reproductive cycle. In particular, mice lacking the clock gene Bmal1 show severe infertility, implying that BMAL1 plays roles in ovulation and luteinization. Here, we examined temporal changes in clock gene expression in the ovary and oviduct before and during gonadotropin-induced follicular growth, ovulation, and luteinization in sexually immature mice. While the oviduct did not show a drastic change in clock gene expression, Bmal1 expression in the ovary was higher than that in control mice during the period from 4 to 16 hr after human chorionic gonadotropin (hCG) administration...
June 19, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Toshihiko Fukuzawa
The periodic albino mutant of Xenopus laevis has been used to study the development of pigment cells because both the retinal pigment epithelium (RPE) and melanophores are affected. In this mutant, "white pigment cells" containing both melanophore-specific and iridophore-specific pigment organelles appear. The present experiments were designed to investigate the structural organization and expression of microphthalmia-associated transcription factor (Mitf) in the mutant since Mitf is known to regulate the development of melanocytes and RPE...
June 19, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Takahide Hibi, Hokuto Ohtsuka, Takafumi Shimasaki, Shougo Inui, Masatoshi Shibuya, Hideki Tatsukawa, Kei Kanie, Yoshihiko Yamamoto, Hirofumi Aiba
Most antiaging factors or life span extenders are associated with calorie restriction (CR). Very few of these factors function independently of, or additively with, CR. In this study, we focused on tschimganine, a compound that was reported to extend chronological life span (CLS). Although tschimganine led to the extension of CLS, it also inhibited yeast cell growth. We acquired a Schizosaccharomyces pombe mutant with a tolerance for tschimganine due to the gene crm1. The resulting Crm1 protein appears to export the stress-activated protein kinase Sty1 from the nucleus to the cytosol even under stressful conditions...
June 14, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Yi-Ting Lai, Chinami Maeda, Kenji Matsuno
The Fourth Asia-Pacific Drosophila Research Conference (APDRC4) was held at the convention center of Osaka University, Osaka, Japan, on May 8-11, 2017. Derived from the Japanese Drosophila Research Conference, the APDRC visited its home for the first time since its launch in 2011 with APDRC1 in Taipei, followed by APDRC2 in Seoul and APDRC3 in Beijing. There were 344 participants from 18 countries, more than half of whom were from abroad (Data S1). Two keynote speakers, Drs. Henry Sun and Daisuke Yamamoto, who have had rich science careers, gave overviews of their research...
June 14, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Masahiro Kumeta, Yulia Panina, Hiroya Yamazaki, Kunio Takeyasu, Shige H Yoshimura
The primary cilium functions as an "antenna" for cell signaling, studded with characteristic transmembrane receptors and soluble protein factors, raised above the cell surface. In contrast to the transmembrane proteins, targeting mechanisms of nontransmembrane ciliary proteins are poorly understood. We focused on a pathogenic mutation that abolishes ciliary localization of retinitis pigmentosa 2 protein and revealed a dual acylation-dependent ciliary targeting pathway. Short N-terminal sequences which contain myristoylation and palmitoylation sites are sufficient to target a marker protein into the cilium in a palmitoylation-dependent manner...
June 13, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Masaaki Iwamoto, Chie Mori, Hiroko Osakada, Takako Koujin, Yasushi Hiraoka, Tokuko Haraguchi
Ciliated protozoa possess two morphologically and functionally distinct nuclei: a macronucleus (MAC) and a micronucleus (MIC). The MAC is transcriptionally active and functions in all cellular events. The MIC is transcriptionally inactive during cell growth, but functions in meiotic events to produce progeny nuclei. Thus, these two nuclei must be distinguished by the nuclear proteins required for their distinct functions during cellular events such as cell proliferation and meiosis. To understand the mechanism of the nuclear transport specific to either MAC or MIC, we identified specific nuclear localization signals (NLSs) in two MAC- and MIC-specific nuclear proteins, macronuclear histone H1 and micronuclear linker histone-like protein (Mlh1), respectively...
June 8, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Ayuko Kubo, Mirai Matsuka, Ryunosuke Minami, Fumika Kimura, Rumi Sakata-Niitsu, Akihiko Kokuryo, Kiichiro Taniguchi, Takashi Adachi-Yamada, Hideki Nakagoshi
Nutrient conditions affect the reproductive potential and lifespan of many organisms through the insulin signaling pathway. Although this is well characterized in female oogenesis, nutrient-dependent regulation of fertility/fecundity in males is not known. Seminal fluid components synthesized in the accessory gland are required for high fecundity in Drosophila males. The accessory gland is composed of two types of binucleated cells: a main cell and a secondary cell (SC). The transcription factors Defective proventriculus (Dve) and Abdominal-B (Abd-B) are strongly expressed in adult SCs, whose functions are essential for male fecundity...
May 30, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Masahiko Itoh, Kazuhiko Nakadate, Taiji Matsusaka, Walter Hunziker, Hiroyuki Sugimoto
Glomerular podocytes in the kidney originate from columnar epithelial cells possessing tight junctions. During podocyte differentiation, tight junctions are replaced by slit diaphragms, which are formed between foot processes and function as a blood filtration barrier. Although the expression of most tight junction components is suppressed during podocyte differentiation, several components, including ZO-1 and ZO-2, are consistently expressed. We recently showed that podocyte-specific deletion of ZO-1 gene impaired slit diaphragm formation, leading to proteinuria and glomerular sclerosis...
May 29, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Takeshi Saji, Michiru Nishita, Hiroyuki Ogawa, Takefumi Doi, Yasuhiro Sakai, Yoshimasa Maniwa, Yasuhiro Minami
Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor prognosis and closely related to exposure to asbestos. MPM is a heterogeneous tumor with three main histological subtypes, epithelioid, sarcomatoid, and biphasic types, among which sarcomatoid type shows the poorest prognosis. The Ror-family of receptor tyrosine kinases, Ror1 and Ror2, is expressed in various types of tumor cells at higher levels and affects their aggressiveness. However, it is currently unknown whether they are expressed in and involved in aggressiveness of MPM...
May 29, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Hirokazu Nakatsumi, Takeru Oka, Tsunaki Higa, Michiko Shirane, Keiichi I Nakayama
Mammalian target of rapamycin complex 1 (mTORC1) kinase is a master regulator of the cellular response to nutrition-related signals such as insulin and amino acids. mTORC1 is activated on the lysosomal membrane and induces phosphorylation of a variety of downstream molecules. We previously showed that activated mTORC1 induces protein phosphatase 2A (PP2A)-mediated dephosphorylation of the transcription factor forkhead box K1 (FOXK1). The mechanism underlying the signal transduction from the cytoplasmic mTORC1 to the nuclear FOXK1 has remained unclear, however, we now show that a nuclear-cytoplasmic transport system is necessary for the mTORC1-FOXK1 signal transduction...
May 29, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Risa Sawada, Toshihiro Aramaki, Shigeru Kondo
The striped pigmentation pattern of zebrafish is determined by the interaction between pigment cells with different colors. Recent studies show the behaviors of pigment cells are substantially different according to the environment. Interestingly, the resulting patterns are almost identical, suggesting a robustness of the patterning mechanism. To know how this robustness originates, we investigated the behavior of melanophores in various environments including different developmental stages, different body positions, and different genetic backgrounds...
May 23, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Shinji Mii, Akiyoshi Hoshino, Atsushi Enomoto, Yoshiki Murakumo, Masako Ito, Akira Yamaguchi, Masahide Takahashi
Osteoporosis is a global public health problem that is increasing along with an aging population. A major determinant of osteoporosis is high bone turnover, which results from osteoclast activation. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, a deficiency that leads to a psoriasis-like skin inflammation in mice. Although the expression of CD109 has been reported in mouse pre-osteoclast cells, its function in osteoclasts in vivo remains largely unknown. To investigate the physiological role of CD109 in bone metabolism, we analyzed bones from wild-type and CD109-deficient adult mice...
May 16, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Takuma Iwasaki, Eiki Yamashita, Atsushi Nakagawa, Atsushi Enomoto, Masashi Tomihara, Shigeki Takeda
Tailed bacteriophages (Caudovirales) are divided into three families: Myoviridae with long contractile tails, Siphoviridae with long noncontractile tails and Podoviridae with short noncontractile tails. All have an icosahedral head with a portal vertex connected to a neck structure followed by a tail. Bacteriophage Mu belongs to the Myoviridae family. Herein, the gp29 portal subunit and neck subunits gp35, gp36 and gp37 of the Mu phage were purified to elucidate their arrangement in the neck. Both gp29 and gp36 were monomeric in solution, like the corresponding subunits of Podoviridae P22 and Siphoviridae SPP1...
May 16, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Naoki Aoyama, Hiroyuki Miyoshi, Hitoshi Miyachi, Masahiro Sonoshita, Masaru Okabe, Makoto Mark Taketo
Jellyfish green fluorescent protein (GFP) and firefly luciferase can serve as versatile tracking markers for identification and quantification of transplanted cancer cells in vivo. However, immune reactions against these markers can hamper the formation of syngraft tumors and metastasis that follows. Here, we report two transgenic (Tg) mouse lines that express nonfunctional mutant marker proteins, namely modified firefly luciferase (Luc2) or enhanced GFP (EGFP). These mice, named as Tg-mLuc2 and Tg-mEGFP, turned out to be immunologically tolerant to the respective tracking markers and thus efficiently accepted syngeneic cancer cells expressing the active forms of the markers...
May 11, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Shigeko Fushimi, Tsutomu Nohno, Hitoshi Nagatsuka, Hironobu Katsuyama
The Wnt/β-catenin signaling and TGFβ signaling pathways play a key role in osteoblast differentiation. The miRNAs play important roles in regulating gene expression at the post-transcriptional level through fine-tuning of protein-encoding gene expression. However, involvement of miRNAs is not established for Wnt3a and TGFβ signaling pathways in osteoblast differentiation. Here, we examined the role of miRNAs expressed differentially after Wnt3a expression during osteoblast differentiation. Over-expression of the Wnt3a gene increased ALP transcription, but decreased Col1, Runx2, and OCN transcription in osteoblastic MC3T3-E1 cells...
May 9, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
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