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Cell Structure and Function

Yuki Oku, Kazuma Murakami, Kazuhiro Irie, Jun Hoseki, Yasuyoshi Sakai
Neuronal cellular accumulation of amyloid beta peptide (Aβ) has been implicated in the pathogenesis of Alzheimer’s disease (AD). Intracellular accumulation of Aβ42, a toxic form of Aβ, was observed as an early event in AD patients. However, its contribution and the cellular mechanism of cell death remained unclear. We herein revealed the mechanism by which Aβ42 incorporated into cells leads to cell death by using chemically synthesized Aβ42 variants. The Aβ42 variant Aβ42 (E22P) which has an increased tendency to oligomerize, accumulated in lysosomes at an earlier stage than wild-type Aβ42, leading to higher ROS production and lysosomal membrane oxidation, and resulting in cell death...
April 12, 2017: Cell Structure and Function
Hitomi Sato, Yoko Shiba, Yuichi Tsuchiya, Michiko Saito, Kenji Kohno
IRE1α plays an important role in the unfolded protein response (UPR), which is activated by the accumulation of unfolded proteins in the endoplasmic reticulum. 4μ8C, a well-known inhibitor of IRE1α RNase activity, is commonly used to analyze IRE1α function during ER stress in cultured mammalian cells. However, the off-target effects of 4μ8C remain elusive. Pancreatic β-cells synthesize a large amount of insulin in response to high glucose stimulation, and IRE1α plays an important role in insulin secretion from pancreatic β-cells...
March 18, 2017: Cell Structure and Function
Junya Hasegawa, Bethany S Strunk, Lois S Weisman
In most eukaryotes, phosphoinositides (PIs) have crucial roles in multiple cellular functions. Although the cellular levels of phosphatidylinositol 5-phosphate (PI5P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) are extremely low relative to some other PIs, emerging evidence demonstrates that both lipids are crucial for the endocytic pathway, intracellular signaling, and adaptation to stress. Mutations that causes defects in the biosynthesis of PI5P and PI(3,5)P2 are linked to human diseases including neurodegenerative disorders...
March 7, 2017: Cell Structure and Function
Mai Taniguchi, Hiderou Yoshida
The capacity of each organelle in eukaryotic cells is tightly regulated in accordance with cellular demands by specific regulatory systems, which are generically termed organelle autoregulation. The Golgi stress response is one of the systems of organelle autoregulation and it augments the capacity of Golgi function if this becomes insufficient (Golgi stress). Recently, several pathways of the mammalian Golgi stress response have been identified, specifically the TFE3, HSP47, and CREB3 pathways. This review summarizes the essential parts of the Golgi stress response from the perspective of the organelle autoregulation...
April 1, 2017: Cell Structure and Function
Mika Horiguchi, Mari Fujioka, Takeshi Kondo, Yoichiro Fujioka, Xinxin Li, Kosui Horiuchi, Aya O Satoh, Prabha Nepal, Shinya Nishide, Asuka Nanbo, Takanori Teshima, Yusuke Ohba
Although the co-development of companion diagnostics with molecular targeted drugs is desirable, truly efficient diagnostics are limited to diseases in which chromosomal translocations or overt mutations are clearly correlated with drug efficacy. Moreover, even for such diseases, few methods are available to predict whether drug administration is effective for each individual patient whose disease is expected to respond to the drug(s). We have previously developed a biosensor based on the principle of Förster resonance energy transfer to measure the activity of the tyrosine kinase BCR-ABL and its response to drug treatment in patient-derived chronic myeloid leukemia cells...
February 2, 2017: Cell Structure and Function
Chunjie Li, Ayako Imanishi, Naoki Komatsu, Kenta Terai, Mutsuki Amano, Kozo Kaibuchi, Michiyuki Matsuda
Genetically-encoded biosensors based on Förster/fluorescence resonance energy transfer (FRET) are versatile tools for studying the spatio-temporal regulation of signaling molecules within not only the cells but also tissues. Perhaps the hardest task in the development of a FRET biosensor for protein kinases is to identify the kinase-specific substrate peptide to be used in the FRET biosensor. To solve this problem, we took advantage of kinase-interacting substrate screening (KISS) technology, which deduces a consensus substrate sequence for the protein kinase of interest...
January 11, 2017: Cell Structure and Function
Ruibin Zhu, Mari Iwabuchi, Keita Ohsumi
Histone chaperones are a group of histone-binding proteins that facilitate the assembly of nucleosomes, the fundamental structural units of chromatin in eukaryotes. In nucleosome assembly, deposition of a histone H3-H4 tetramer onto DNA is the first and critical step, which is mediated by the histone chaperones HIRA and CAF-1. HIRA and CAF-1 are reportedly involved in DNA replication independent (RI) and replication coupled nucleosome assembly, respectively. However, the mechanisms by which they mediate histone deposition remain unclear...
2017: Cell Structure and Function
Daisuke Muramatsu, Hiroshi Kimura, Kaoru Kotoshiba, Makoto Tachibana, Yoichi Shinkai
Pericentric regions form epigenetically organized, silent heterochromatin structures that accumulate histone H3 lysine 9 tri-methylation (H3K9me3) and heterochromatin protein 1 (HP1), a methylated H3K9-binding protein. At pericentric regions, Suv39h is the major enzyme that generates H3K9me3. Suv39h also interacts directly with HP1. However, the importance of HP1 interaction for Suv39h-mediated H3K9me3 formation at the pericentromere is not well characterized. To address this question, we introduced HP1 binding-defective, N-terminally truncated mouse Suv39h1 (ΔN) into Suv39h-deficient cells...
December 3, 2016: Cell Structure and Function
Seiji Yamamoto, Erika Azuma, Masashi Muramatsu, Takeru Hamashima, Yoko Ishii, Masakiyo Sasahara
Over the past decade, many studies have been conducted on extracellular vesicles (EVs) in the fields of basic and clinical research. EVs are small sized membranous vesicles generated from many type of cells upon activation by environmental stresses such as heat, hypoxia, and irradiation. EVs theoretically consist of microparticles/microvesicles, exosomes, and apoptotic bodies by different productive mechanisms. Clinically, EVs are observed in the blood stream of patients suffering from acute and chronic inflammation evoked by various diseases, and number of EVs in blood flow is often dependent on the inflammatory status and severity of the diseases...
November 25, 2016: Cell Structure and Function
Mika Toya, Masatoshi Takeichi
Polarized epithelial cells contain a characteristic array of microtubules in which non-centrosomal microtubules are aligned along the apical-to-basal axis of the cell with their minus ends oriented towards the apical pole. Although this unique orientation of microtubules was discovered in the late 1980s, how this orientation is established remains unresolved partly because of limited information about molecular factors that regulate the minus ends of non-centrosomal microtubules. Recent studies, however, identified novel minus end-associated proteins, revealing mechanisms by which the polarized arrays of microtubules are established in epithelial cells...
October 15, 2016: Cell Structure and Function
Kazuki Motomura, Frédéric Berger, Tomokazu Kawashima, Tetsu Kinoshita, Tetsuya Higashiyama, Daisuke Maruyama
In flowering plants, fertilization of the central cell gives rise to an embryo-nourishing endosperm. Recently, we reported that the endosperm absorbs the adjacent synergid cell through a cell-fusion, terminating the pollen tube guidance by a rapid inactivation of the synergid cell. Although this synergid-endosperm fusion (SE fusion) initiates soon after fertilization, it was still unknown whether the triggers of SE fusion are stimuli during fertilization or other seed developmental processes. To further dissect out the SE fusion process, we investigated the SE fusion in an Arabidopsis mutant defective for MULTICOPY SUPPRESSOR OF IRA1 (MSI1), a subunit of the polycomb repressive complex 2 (PRC2)...
August 23, 2016: Cell Structure and Function
Yoshimitsu Yura, Mutsuki Amano, Mikito Takefuji, Tomohiro Bando, Kou Suzuki, Katsuhiro Kato, Tomonari Hamaguchi, Md Hasanuzzaman Shohag, Tetsuya Takano, Yasuhiro Funahashi, Shinichi Nakamuta, Keisuke Kuroda, Tomoki Nishioka, Toyoaki Murohara, Kozo Kaibuchi
Protein phosphorylation plays an important role in the physiological regulation of cardiac function. Myocardial contraction and pathogenesis of cardiac diseases have been reported to be associated with adaptive or maladaptive protein phosphorylation; however, phosphorylation signaling in the heart is not fully elucidated. We recently developed a novel kinase-interacting substrate screening (KISS) method for exhaustive screening of protein kinase substrates, using mass spectrometry and affinity chromatography...
August 23, 2016: Cell Structure and Function
Mai Taniguchi, Kanae Sasaki-Osugi, Masaya Oku, Shogo Sawaguchi, Soichiro Tanakura, Yumeto Kawai, Sadao Wakabayashi, Hiderou Yoshida
The Golgi stress response is a homeostatic mechanism that controls the capacity of the Golgi apparatus in accordance with cellular demands. When the capacity of the Golgi apparatus becomes insufficient (Golgi stress), transcription levels of Golgi-related genes encoding glycosylation enzymes, a Golgi structural protein, and components of vesicular transport are upregulated through a common cis-acting enhancer-the Golgi apparatus stress response element (GASE). Here, we identified the transcription factor MLX as a GASE-binding protein...
July 30, 2016: Cell Structure and Function
Gembu Maryu, Michiyuki Matsuda, Kazuhiro Aoki
The Ras-ERK pathway controls cell proliferation and differentiation, whereas the PI3K-Akt pathway plays a role in the process of cell-cycle progression and cell survival. Both pathways are activated by many stimuli such as epidermal growth factor (EGF), and coordinately regulate each other through cross-talk. However, it remains unclear how cells accommodate the dynamics and interplay between the Ras-ERK and PI3K-Akt pathways to regulate cell-fate decisions, mainly because of the lack of good tools to visualize ERK and Akt activities simultaneously in live cells...
July 22, 2016: Cell Structure and Function
Morié Ishida, Mai E Oguchi, Mitsunori Fukuda
Rab small GTPases are highly conserved master regulators of membrane traffic in all eukaryotes. The same as the activation and inactivation of other small GTPases, the activation and inactivation of Rabs are tightly controlled by specific GEFs (guanine nucleotide exchange factors) and GAPs (GTPase-activating proteins), respectively. Although almost all Rab-GAPs reported thus far have a TBC (Tre-2/Bub2/Cdc16)/Rab-GAP domain in common, recent accumulating evidence has indicated the existence of a number of structurally unrelated types of Rab-GEFs, including DENN proteins, VPS9 proteins, Sec2 proteins, TRAPP complexes, heterodimer GEFs (Mon1-Ccz1, HPS1-HPS4 (BLOC-3 complex), Ric1-Rgp1 and Rab3GAP1/2), and other GEFs (e...
July 9, 2016: Cell Structure and Function
Miki Yamamoto-Hino, Satoshi Goto
The Toll pathway regulates innate immunity in insects and vertebrates. The Drosophila Toll receptor is activated by a processed form of a ligand, Spätzle. Spätzle-processing enzyme (SPE) is the only enzyme identified to date that functions in converting Spätzle to an active form during the immune response. In the present study, Toll activation induced by immune challenge was almost suppressed in spätzle mutant larvae and adults, whereas it was present in SPE mutant larvae challenged with Micrococcus luteus and adults challenged with Bacillus subtilis...
May 7, 2016: Cell Structure and Function
Ayane Sonoda, Chika Okimura, Yoshiaki Iwadate
Fish epidermal keratocytes maintain an overall fan shape during their crawling migration. The shape-determination mechanism has been described theoretically and experimentally on the basis of graded radial extension of the leading edge, but the relationship between shape and traction forces has not been clarified. Migrating keratocytes can be divided into fragments by treatment with the protein kinase inhibitor staurosporine. Fragments containing a nucleus and cytoplasm behave as mini-keratocytes and maintain the same fan shape as the original cells...
March 26, 2016: Cell Structure and Function
Souichi Oe, Harukata Miki, Wataru Nishimura, Yasuko Noda
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor critical for synaptic plasticity, neuronal development and neurite extension. BDNF mRNA is transported to dendrites and axons, where it is expressed locally. We previously reported that dendritic targeting elements in the BDNF 3' UTR are necessary for dendritic transport and interact with cytoplasmic polyadenylation element binding protein 1. Here, we demonstrated that the short 3' UTR directs local translation of BDNF and that locally synthesized BDNF exists in a novel compartment that does not co-localize with markers of endosomes, endoplasmic reticulum, Golgi or the trans-Golgi network...
March 26, 2016: Cell Structure and Function
Naoji Toyota, Chiaki Fujitsuka, Goushi Ishibashi, Lucia S Yoshida, Hiromi Takano-Ohmuro
Tropomyosin (TPM) localizes along F-actin and, together with troponin T (TnT) and other components, controls calcium-sensitive muscle contraction. The role of the TPM isoform (TPM4α) that is expressed in embryonic and adult cardiac muscle cells in chicken is poorly understood. To analyze the function of TPM4α in myofibrils, the effects of TPM4α-suppression were examined in embryonic cardiomyocytes by small interference RNA transfection. Localization of myofibril proteins such as TPM, actin, TnT, α-actinin, myosin and connectin was examined by immunofluorescence microscopy on day 5 when almost complete TPM4α-suppression occurred in culture...
2016: Cell Structure and Function
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2016: Cell Structure and Function
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