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Biology of the Cell

Junhui He, Mingchong Sun, Huaizhen Geng, Sujian Tian
BACKGROUND INFORMATION: To characterize Linc00518 expression in prostate cancer and elucidate the potential mechanistic involvement in paclitaxel resistance. The relative expression of Linc00518 and miR-216b-5p was determined by real-time PCR. The regulatory effect of miR-216b-5p on either Linc00518 or GATA6 was interrogated with luciferase reporter assay. The endogenous GATA6 protein was analyzed by western blotting. The cell viability was measured by MTT assay and IC50 of paclitaxel was calculated through cell counting...
November 21, 2018: Biology of the Cell
Lei Zhu, Hao Liu, Yawen Chen, Xiumin Yan, Xueliang Zhu
BACKGROUND INFORMATION: In the "9+2"-type motile cilia, radial spokes (RSs) protruded from the nine peripheral microtubule doublets surround and interact with the central pair (CP) apparatus to regulate ciliary beat. RSPH9 is the human homologue of the essential protozoan RS head protein Rsp9. Its mutations in human primary ciliary dyskinesia patients, however, cause CP loss in a small portion of airway cilia without affecting the ciliary localization of other head proteins...
November 1, 2018: Biology of the Cell
Chang Seong Kim, In Jin Kim, Joon Seok Choi, Eun Hui Bae, Seong Kwon Ma, Soo Wan Kim
BACKGROUND INFORMATION: Tubulointerstitial fibrosis is the end-point of chronic kidney diseases. Tamoxifen, a selective oestrogen receptor (ER) modulator, attenuates renal fibrosis, by regulating the transforming growth factor (TGF)-β/Smad signalling. Src and phosphoinositide 3-kinase (PI3K)/Akt pathways play critical roles in the pathogenesis of renal fibrosis. However, the activation of the non-canonical TGF-β signalling in renal fibrosis after treatment with tamoxifen remains unclear...
October 10, 2018: Biology of the Cell
Emma Madden, Susan E Logue, Sandra J Healy, Serge Manie, Afshin Samali
Tumour cells endure both oncogenic and environmental stresses during cancer progression. Transformed cells must meet increased demands for protein and lipid production needed for rapid proliferation and must adapt to exist in an oxygen- and nutrient-deprived environment. To overcome such challenges, cancer cells exploit intrinsic adaptive mechanisms such as the unfolded protein response (UPR). The UPR is a pro-survival mechanism triggered by accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER), a condition referred to as ER stress...
October 10, 2018: Biology of the Cell
F Delom, A Nazaraliyev, D Fessart
In recent years, the discovery of "tumor niche", a microenvironment that favors tumor development has changed our perspective of cancer. This microenvironment generated by the tumor cells itself and surrounding cells, is capable of providing essential elements for its growth. Consequently, the homeostasis of the Secretory Pathway (SP) has become an essential player in cancer development. The SP not only promotes cellular adaptation to protein misfolding due to oncogenic transformation or challenging tumor niche but also allows tumor cells to produce specific secretomes...
September 21, 2018: Biology of the Cell
Joseph E Chambers, Jennifer A Dickens, Stefan J Marciniak
An important function of the endoplasmic reticulum (ER) is to serve as a site of secretory protein folding. When the accumulation of misfolded proteins threatens to disturb luminal homoeostasis, the cell is said to experience ER stress. By contrast, the accumulation of well-folded proteins inside the ER leads to a distinct form of strain called ER overload. The serpins comprise a large family of proteins whose folding has been studied in great detail. Some mutant serpins misfold to cause ER stress, whereas others fold but then polymerise to cause ER overload...
November 2018: Biology of the Cell
Caroline Demangel, Stephen High
Infection with Mycobacterium ulcerans results in a necrotising skin disease known as a Buruli ulcer, the pathology of which is directly linked to the bacterial production of the toxin mycolactone. Recent studies have identified the protein translocation machinery of the endoplasmic reticulum (ER) membrane as the primary cellular target of mycolactone, and shown that the toxin binds to the core subunit of the Sec61 complex. Mycolactone binding strongly inhibits the capacity of the Sec61 translocon to transport newly synthesised membrane and secretory proteins into and across the ER membrane...
November 2018: Biology of the Cell
Maurício Tavares Tamborindeguy, Bibiana Franzen Matte, Grasieli de Oliveira Ramos, Alessandro Menna Alves, Lisiane Bernardi, Marcelo Lazzaron Lamers
BACKGROUND INFORMATION: Cell migration requires the coordinated activation of structural and signalling molecules, such as the RhoGTPase Rac1. It is known that the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex assembly, which generates reactive oxygen species (ROS) at the cell membrane, also relies on Rac1 activation, indicating a possible effect of ROS during cell migration. In this study, we evaluated the effect of NADPH-oxidase-derived ROS on the migration process...
October 2018: Biology of the Cell
Fei Xu, Shouhong Guang, Xuezhu Feng
Epigenetic information can be inherited over multiple generations, which is termed as transgenerational epigenetic inheritance (TEI). Although the mechanism(s) of TEI remains poorly understood, noncoding RNAs have been demonstrated to play important roles in TEI. In many eukaryotes, double-stranded RNA (dsRNA) triggers the silencing of cellular nucleic acids that exhibit sequence homology to the dsRNA via a process termed RNA interference (RNAi). In Caenorhabditis elegans, dsRNA-directed gene silencing is heritable and can persist for a number of generations after its initial induction...
October 2018: Biology of the Cell
Morgan Gallazzini, Nicolas Pallet
Chronic kidney disease (CKD) affects millions of persons worldwide and constitutes a major public health problem. Therefore, understanding the molecular basis of CKD is a key challenge for the development of preventive and therapeutic strategies. A major contributor to chronic histological damage associated with CKD is acute kidney injury (AKI). At the cellular level, kidney injuries are associated with microenvironmental alterations, forcing cells to activate adaptive biological processes that eliminate the stressor and generate alarm signals...
September 2018: Biology of the Cell
Timothy J Bergmann, Maurizio Molinari
Study of the unfolded protein responses (UPR) is mainly addressed by challenging eukaryotic cells with chemical compounds that impair calcium, redox or glycan homeostasis. These dramatically alter the endoplasmic reticulum (ER) environment and function, but also trigger pleiotropic effects that may result in multi-organellar failure and cell death. Recent works showed that UPR induced by the accumulation of unfolded polypeptides in the ER lumen drastically differs from chemically induced UPR. Unfolded proteins are tolerated by cells, which activate a finely tuned UPR without entering apoptotic programs...
September 2018: Biology of the Cell
Ruibai Luo, Pei-Wen Chen, Jean-Cheng Kuo, Lisa Jenkins, Xiaoying Jian, Clare M Waterman, Paul A Randazzo
BACKGROUND INFORMATION: ARAP2, an Arf GTPase-activating protein (Arf GAP) that binds to adaptor protein with PH domain, PTB domain and leucine zipper motifs 1 (APPL1), regulates focal adhesions (FAs). APPL1 affects FA dynamics by regulating Akt. Here, we tested the hypothesis that ARAP2 affects FAs in part by regulating Akt through APPL1. RESULTS: We found that ARAP2 controlled FA dynamics dependent on its enzymatic Arf GAP activity. In some cells, ARAP2 also regulated phosphoAkt (pAkt) levels...
August 25, 2018: Biology of the Cell
Julie Di Martino, Patrice Mascalchi, Philippe Legros, Sabrina Lacomme, Etienne Gontier, Paulette Bioulac-Sage, Charles Balabaud, Violaine Moreau, Frédéric Saltel
BACKGROUND INFORMATION: Liver sinusoidal endothelial cells (LSECs) possess fenestrae, open transcellular pores with an average diameter of 100 nm. These fenestrae allow for the exchange between blood and hepatocytes. Alterations in their number or diameter in liver diseases have important implications for hepatic microcirculation and function. Although decades of studies, fenestrae are still observed into fixed cells and we have poor knowledge of their dynamics. RESULTS: Using stimulated emission depletion (STED) super-resolution microscopy, we have established a faster and simplest method to observe and quantify fenestrae...
July 2018: Biology of the Cell
Maria Francesca Armentano, Marianna Caterino, Rocchina Miglionico, Angela Ostuni, Maria Carmela Pace, Flora Cozzolino, Maria Monti, Luigi Milella, Monica Carmosino, Piero Pucci, Faustino Bisaccia
BACKGROUND INFORMATION: Up-regulated Gene clone 7 (URG7) is an ER resident protein, whose expression is up-regulated in the presence of hepatitis B virus X antigen (HBxAg) during HBV infection. In virus-infected hepatocytes, URG7 shows an anti-apoptotic activity due to the PI3K/AKT signalling activation, does not seem to have tumorigenic properties, but it appears to promote the development and progression of fibrosis. However, the molecular mechanisms underlying URG7 activity remain largely unknown...
July 2018: Biology of the Cell
Elmina Mammadova-Bach, Tristan Rupp, Caroline Spenlé, Ivo Jivkov, Pattabhiraman Shankaranarayanan, Annick Klein, Laura Pisarsky, Agnès Méchine-Neuville, Gérard Cremel, Michèle Kedinger, Olivier De Wever, Noona Ambartsumian, Sylvie Robine, Erwan Pencreach, Dominique Guenot, Patricia Simon-Assmann, Jacky G Goetz, Gertraud Orend, Olivier Lefebvre
BACKGROUND INFORMATION: Tumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma. RESULTS: By employing mouse models expressing high and low levels of the laminin α1 chain (LMα1), we highlighted its implication in a tumor-stroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth...
June 15, 2018: Biology of the Cell
Girisaran Gangatharan, Sylvie Schneider-Maunoury, Marie Anne Breau
Neuronal circuits, the functional building blocks of the nervous system, assemble during development through a series of dynamic processes including the migration of neurons to their final position, the growth and navigation of axons and their synaptic connection with target cells. While the role of chemical cues in guiding neuronal migration and axonal development has been extensively analysed, the contribution of mechanical inputs, such as forces and stiffness, has received far less attention. In this article, we review the in vitro and more recent in vivo studies supporting the notion that mechanical signals are critical for multiple aspects of neuronal circuit assembly, from the emergence of axons to the formation of functional synapses...
June 2018: Biology of the Cell
Patrick von Morgen, Tomas Lidak, Zuzana Horejsi, Libor Macurek
BACKGROUND INFORMATION: Repair of damaged DNA is essential for maintaining genomic stability. TP53-binding protein 1 (53BP1) plays an important role in repair of the DNA double-strand breaks. Nuclear localisation of 53BP1 depends on importin β and nucleoporin 153, but the type and location of 53BP1 nuclear localisation signal (NLS) have yet to be determined. RESULTS: Here, we show that nuclear import of 53BP1 depends on two basic regions, namely 1667-KRK-1669 and 1681-KRGRK-1685, which are both needed for importin binding...
June 2018: Biology of the Cell
Qing Wang, Hsin-Sheng Yang
Programmed cell death 4 (Pdcd4), a tumour suppressor, is frequently down-regulated in various types of cancer. Pdcd4 has been demonstrated to efficiently suppress tumour promotion, progression and proliferation. The biochemical function of Pdcd4 is a protein translation inhibitor. Although the fact that Pdcd4 inhibits protein translation has been known for more than a decade, the mechanism by which Pdcd4 controls tumorigenesis through translational regulation of its target genes is still not fully understood...
May 28, 2018: Biology of the Cell
Silvia Ravera, Maria Grazia Signorello, Martina Bartolucci, Sara Ferrando, Lucia Manni, Federico Caicci, Daniela Calzia, Isabella Panfoli, Alessandro Morelli, Giuliana Leoncini
BACKGROUND INFORMATION: Energy demand in human platelets is very high, to carry out their functions. As for most human cells, the aerobic metabolism represents the primary energy source in platelets, even though mitochondria are negligibly represented. Following the hypothesis that other structures could be involved in chemical energy production, in this work, we have investigated the functional expression of an extramitochondrial aerobic metabolism in platelets. RESULTS: Oximetric and luminometric analyses showed that platelets consume large amounts of oxygen and produce ATP in the presence of common respiring substrates, such as pyruvate + malate or succinate, although morphological electron microscopy analysis showed that these contain few mitochondria...
May 2018: Biology of the Cell
Makoto Nakashima, Mariko Watanabe, Kaoru Uchimaru, Ryouichi Horie
BACKGROUND INFORMATION: CD30, which is characteristically expressed in classical Hodgkin lymphoma (cHL), is thought to transduce signals by ligation of trimerised CD30 ligand (CD30L) on the surface of surrounding cells and recruitment of downstream molecules. In this report, we propose a new mechanism for CD30 signalling by its ligand. We prepared two stable transformants, CHO cells expressing CD30L fused to mCherry and HeLa cells expressing CD30 fused to GFP. RESULTS: Co-culture of these cells triggered clustering of CD30 and CD30L at the cellular interface, formation of multiple CD30L-CD30 complexes, internalisation of these complexes with a portion of the plasma membrane into the HeLa cells, and intracellular transport to the lysosomal compartment...
May 2018: Biology of the Cell
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