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Membrane association

Colin R Jefcoate, Jinwoo Lee
Cholesterol is an important regulator of cell signaling, both through direct impacts on cell membranes and through oxy-metabolites that activate specific receptors (steroids, hydroxy-cholesterols, bile acids). Cholesterol moves slowly through and between cell membranes with the assistance of specific binding proteins and transfer processes. The prototype cholesterol regulator is the Steroidogenesis Acute Regulatory (STAR), which moves cholesterol into mitochondria, where steroid synthesis is initiated by cytochrome P450 11A1 in multiple endocrine cell types...
May 2018: Journal of Molecular Endocrinology
Daniele Avanzato, Emanuela Pupo, Nadia Ducano, Claudio Isella, Giovanni Bertalot, Chiara Luise, Salvatore Pece, Alejandra Bruna, Oscar M Rueda, Carlos Caldas, Pier Paolo Di Fiore, Anna Sapino, Letizia Lanzetti
USP6NL, also named RN-tre, is a GTPase activating protein (GAP) involved in control of endocytosis and signal transduction. Here we report that USP6NL is overexpressed in breast cancer (BC), mainly of the basal-like/integrative cluster 10 subtype. Increased USP6NL levels were accompanied by gene amplification and were associated with worse prognosis in the METABRIC dataset, retaining prognostic value in multivariable analysis. High levels of USP6NL in BC cells delayed endocytosis and degradation of the epidermal growth factor receptor (EGFR), causing chronic AKT activation...
April 24, 2018: Cancer Research
Cristiana Borrelli, Biancamaria Ricci, Elisabetta Vulpis, Cinzia Fionda, Maria Rosaria Ricciardi, Maria Teresa Petrucci, Laura Masuelli, Agnese Peri, Marco Cippitelli, Alessandra Zingoni, Angela Santoni, Alessandra Soriani
Treatment of multiple myeloma (MM) cells with sub-lethal doses of genotoxic drugs leads to senescence and results in increased NK cell recognition and effector functions. Herein we demonstrated that doxorubicin- and melphalan-treated senescent cells display increased expression of IL15, a cytokine involved in NK cell activation, proliferation, and maturation. IL15 up-regulation was evident at the mRNA and protein level, both in MM cell lines and malignant plasma cells (PCs) from patients' bone marrow (BM) aspirates...
April 24, 2018: Cancer Immunology Research
Ineta Popēna, Artūrs Ābols, Līga Saulīte, Kārlis Pleiko, Elīna Zandberga, Kaspars Jēkabsons, Edgars Endzeliņš, Alicia Llorente, Aija Linē, Una Riekstiņa
BACKGROUND: Macrophages are one of the most important players in the tumor microenvironment. The polarization status of tumor associated macrophages into a pro-inflammatory type M1 or anti-inflammatory type M2 may influence cancer progression and patient survival. Extracellular vesicles (EVs) are membrane-bound vesicles containing different biomolecules that are involved in cell to cell signal transfer. Accumulating evidence suggests that cancer-derived EVs are taken up by macrophages and modulate their phenotype and cytokine profile...
April 24, 2018: Cell Communication and Signaling: CCS
Janja Kuharić, Kristina Grabusic, Vlatka Sotosek Tokmadzic, Sanja Štifter, Ksenija Tulić, Olga Shevchuk, Pero Lučin, Alan Šustić
Extracellular vesicles (EVs) are membranous nanostructures that can indicate undergoing processes in organs and thus help in diagnostics and prognostics. They are secreted by all cells, contained in body fluids and able to transfer proteins, lipids and nucleic acids to distant cells. Intracranial EVs were shown to change their composition after severe traumatic brain injury (TBI) and therefore to have biomarker potential to evaluate brain events. However, properties of intracranial EVs early after TBI have not been characterized...
April 25, 2018: Journal of Neurotrauma
Xu Yang, Yiling Ding, Mengyuan Yang, Ling Yu, Yun Hu, Yali Deng
BACKGROUND/AIMS: Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that is characterised by a high incidence of hypertension and proteinuria. Podocytes are involved in the formation of a split membrane, which is the last barrier preventing the leakage of protein into the urine. Nestin, a cytoskeleton protein, is expressed stably in podocytes. However, the association between the Nestin concentration in urine and the progression of PE and the role of Nestin in PE remains unclear...
April 19, 2018: Kidney & Blood Pressure Research
Yuri Choi, Yeo-Jin Won, Sojeong Lee, Ahrong Kim, Younggeum Kim, Won-Young Park, Hong-Jae Jo, Geun Am Song, Chae Hwa Kwon, Do Youn Park
NTRK1 gene fusions, the targets of multikinase inhibitors, are promising therapeutic targets for colorectal cancer (CRC). However, screening methods for detecting NTRK1 gene fusions in CRC tissues have not been reported. In this study, we investigated the potential use of immunohistochemistry (IHC) for detecting NTRK1 gene fusions. We performed and compared IHC with fluorescence in situ hybridization (FISH) in 80 CRC patients. TrkA immunostaining was observed to be both membranous and cytoplasmic and was scored semiquantitatively using staining intensity and proportions...
April 21, 2018: Translational Oncology
Yang Liu, Jiawei Yan, Cao Sun, Guo Li, Sirui Li, Luwei Zhang, Cuixia Di, Lu Gan, Yupei Wang, Rong Zhou, Jing Si, Hong Zhang
Carbon ion therapy is a promising modality in radiotherapy to treat tumors, however, a potential risk of induction of late normal tissue damage should still be investigated and protected. The aim of the present study was to explore the long-term cognitive deficits provoked by a high-linear energy transfer (high-LET) carbon ions in mice by targeting to hippocampus which plays a crucial role in memory and learning. Our data showed that, one month after 4 Gy carbon ion exposure, carbon ion irradiation conspicuously resulted in the impaired cognitive performance, neurodegeneration and neuronal cell death, as well as the reduced mitochondrial integrity, the disrupted activities of tricarboxylic acid cycle flux and electron transport chain, and the depressed antioxidant defense system, consequently leading to a decline of ATP production and persistent oxidative damage in the hippocampus region...
April 14, 2018: Redox Biology
Ferdi Ridvan Kiral, Friederike Elisabeth Kohrs, Eugene Jennifer Jin, Peter Robin Hiesinger
Defects in membrane trafficking are hallmarks of neurodegeneration. Rab GTPases are key regulators of membrane trafficking. Alterations of Rab GTPases, or the membrane compartments they regulate, are associated with virtually all neuronal activities in health and disease. The observation that many Rab GTPases are associated with neurodegeneration has proven a challenge in the quest for cause and effect. Neurodegeneration can be a direct consequence of a defect in membrane trafficking. Alternatively, changes in membrane trafficking may be secondary consequences or cellular responses...
April 23, 2018: Current Biology: CB
Jacopo Meldolesi
Exosomes and ectosomes, two distinct types of extracellular vesicles generated by all types of cell, play key roles in intercellular communication. The formation of these vesicles depends on local microdomains assembled in endocytic membranes for exosomes and in the plasma membrane for ectosomes. These microdomains govern the accumulation of proteins and various types of RNA associated with their cytosolic surface, followed by membrane budding inward for exosome precursors and outward for ectosomes. A fraction of endocytic cisternae filled with vesicles - multivesicular bodies - are later destined to undergo regulated exocytosis, leading to the extracellular release of exosomes...
April 23, 2018: Current Biology: CB
Jana Link, Dimitra Paouneskou, Maria Velkova, Anahita Daryabeigi, Triin Laos, Sara Labella, Consuelo Barroso, Sarai Pacheco Piñol, Alex Montoya, Holger Kramer, Alexander Woglar, Antoine Baudrimont, Sebastian Mathias Markert, Christian Stigloher, Enrique Martinez-Perez, Alexander Dammermann, Manfred Alsheimer, Monique Zetka, Verena Jantsch
Meiotic chromosome movement is important for the pairwise alignment of homologous chromosomes, which is required for correct chromosome segregation. Movement is driven by cytoplasmic forces, transmitted to chromosome ends by nuclear membrane-spanning proteins. In animal cells, lamins form a prominent scaffold at the nuclear periphery, yet the role lamins play in meiotic chromosome movement is unclear. We show that chromosome movement correlates with reduced lamin association with the nuclear rim, which requires lamin phosphorylation at sites analogous to those that open lamina network crosslinks in mitosis...
April 23, 2018: Developmental Cell
Zhihao Sun, Jeffrey L Brodsky
Protein homeostasis in the secretory pathway is maintained by a hierarchy of quality control checkpoints, including endoplasmic reticulum-associated degradation (ERAD), which leads to the destruction of misfolded proteins in the ER, as well as post-ER proteolysis. Although most aberrant proteins are degraded by ERAD, some misfolded proteins escape the ER and are degraded instead by lysosomal/vacuolar proteases. To date, it remains unclear how misfolded membrane proteins are selected for these different fates...
April 24, 2018: Molecular Biology of the Cell
Yan Zhu, Tobias Czauderna, Jinxin Zhao, Matthias Klapperstueck, Mohd Hafidz Mahamad Maifiah, Mei-Ling Han, Jing Lu, Björn Sommer, Tony Velkov, Trevor Lithgow, Jiangning Song, Falk Schreiber, Jian Li
Background: Pseudomonas aeruginosa often causes multidrug-resistant infections in immunocompromised patients, and polymyxins are often used as the last-line therapy. Alarmingly, resistance to polymyxins has been increasingly reported worldwide recently. To rescue this last-resort class of antibiotics, it is necessary to systematically understand how P. aeruginosa alters its metabolism in response to polymyxin treatment, thereby facilitating the development of effective therapies. To this end, a genome-scale metabolic model (GSMM) was used to analyze bacterial metabolic changes at the systems level...
April 1, 2018: GigaScience
Wenqin Xiao, Bo Li, Xi Sun, Dandan Yu, Yongsheng Xie, Huiqun Wu, Shuaikang Chang, Yunfei Zhou, Houcai Wang, Xiucai Lan, Zhijian Xu, Jumei Shi, Weiliang Zhu
DCZ3301, a novel aryl-guanidino compound, was previously found to have potent anti-tumor activity in myeloma and B-cell lymphoma. In the present study, we investigated the effects of DCZ3301 on T-cell leukemia/lymphoma cells both in vitro and in vivo via cell proliferation, cell cycle analysis, apoptosis assay, mitochondrial membrane potential (MMP) assay, western blot analysis and tumor xenograft models. We found that DCZ3301 inhibited the viability of T-cell leukemia/lymphoma cells in a dose- and time-dependent manner...
April 23, 2018: Acta Biochimica et Biophysica Sinica
Sholeem Griffin, Gareth D Healey, I Martin Sheldon
Preventing postpartum uterine disease depends on the ability of endometrial cells to tolerate the presence of the bacteria that invade the uterus after parturition. Postpartum uterine disease and endometrial pathology in cattle is most associated with the pathogen Trueperella pyogenes. Trueperella pyogenes secretes a cholesterol-dependent cytolysin, pyolysin, which causes cytolysis by forming pores in the plasma membrane of endometrial stromal cells. The aim of the present study was to identify cell-intrinsic pathways that increase bovine endometrial stromal cell tolerance to pyolysin...
April 24, 2018: Biology of Reproduction
Yuxin Qian, Fan Qi, Qi Chen, Qiang Zhang, Zhongqian Qiao, Si Zhang, Ting Wei, Qian Yu, Shan Yu, Zhengwei Mao, Changyou Gao, Yiru Ding, Yanyong Cheng, Chenyu Jin, Hexin Xie, Runhui Liu
Methicillin-resistant Staphylococcus aureus (MRSA) has been one of the major nosocomial pathogens to cause frequent and serious infections that are associated with various biomedical surfaces. This study demonstrated that surface modified with host defense peptide-mimicking β-peptide polymer, has surprisingly high bactericidal activities against Escherichia coli ( E. coli) and MRSA. As surface-tethered β-peptide polymers cannot move freely to adopt the collaborative interactions with bacterial membrane and are too short to penetrate the cell envelop, we proposed a mode of action by diffusing away the cell membrane-stabilizing divalent ions, Ca2+ and Mg2+ ...
April 24, 2018: ACS Applied Materials & Interfaces
Nadia Peerboom, Eneas Schmidt, Edward Trybala, Stephan Block, Tomas Bergström, Hudson P Pace, Marta Bally
Discovery and development of new antiviral therapies essentially rely on two key factors: an in-depth understanding of the mechanisms involved in viral infection and the development of fast and versatile drug screening platforms. To meet those demands, we present a biosensing platform to probe virus-cell membrane interactions on a single particle level. Our method is based on the formation of supported lipid bilayers from cell membrane material. Using total internal reflection fluorescence microscopy, we report the contribution of viral and cellular components to the interaction kinetics of herpes simplex virus type 1 with the cell membrane...
April 24, 2018: ACS Infectious Diseases
S Elizabeth Norred, Patrick M Caveney, Gaurav Chauhan, Lauren K Collier, C Patrick Collier, Steven M Abel, Michael L Simpson
Recent superresolution microscopy studies in E. coli demonstrate that the cytoplasm has highly variable local concentrations where macromolecular crowding plays a central role in establishing membrane-less compartmentalization. This spatial inhomogeneity significantly influences molecular transport and association processes central to gene expression. Yet, little is known about how macromolecular crowding influences gene expression bursting-the episodic process where mRNA and proteins are produced in bursts...
April 25, 2018: ACS Synthetic Biology
Hua Xu, Fayez K Ghishan, Pawel R Kiela
The Slc9 family of Na+ /H+ exchangers (NHEs) plays a critical role in electroneutral exchange of Na+ and H+ in the mammalian intestine as well as other absorptive and secretory epithelia of digestive organs. These transport proteins contribute to the transepithelial Na+ and water absorption, intracellular pH and cellular volume regulation as well as the electrolyte, acid-base, and fluid volume homeostasis at the systemic level. They also influence the function of other membrane transport mechanisms, affect cellular proliferation and apoptosis as well as cell migration, adherence to the extracellular matrix, and tissue repair...
March 26, 2018: Comprehensive Physiology
Shu-Yin Xu, Juan Jiang, Aihua Pan, Yan Cai, Xiao-Xin Yan
Age-related dementias are now a major mortality factor among most human populations in the world, with Alzheimer's disease (AD) being the leading dementia-causing neurodegenerative disease. The pathogenic mechanism underlying dementia disorders, and AD in specific, remained largely unclear. Efforts to develop drugs targeting the major disease hallmark lesions, such as amyloid and tangle pathologies, have been unsuccessful so far. The vacuolar protein sorting 10p (Vps10p) family plays a critical role in membrane signal transduction and protein sorting and trafficking between intracellular compartments...
April 24, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
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