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Bojie Cong, Shizue Ohsawa, Tatsushi Igaki
Epithelial cancer tissues often possess polyploid giant cells, which are thought to be highly oncogenic. However, the mechanisms by which polyploid giant cells are generated in tumor tissues and how such cells contribute to tumor progression remain elusive. We previously noticed in Drosophila imaginal epithelium that cells mutant for the endocytic gene rab5 exhibit enlarged nuclei. Here we find that mutations in endocytic 'neoplastic tumor-suppressor' genes, such as rab5, vps25, erupted, or avalanche result in generation of polyploid giant cells...
March 14, 2018: Oncogene
Jing Shi, Ran Xiong, Tao Zhou, Peiyi Su, Xihe Zhang, Xusheng Qiu, Hongmei Li, Sunan Li, Changqing Yu, Bin Wang, Chan Ding, Thomas E Smithgall, Yong-Hui Zheng
The primate lentiviral accessory protein Nef downregulates CD4 and MHC-I from the cell surface via independent endosomal trafficking pathways to promote viral pathogenesis. In addition, Nef antagonizes a novel restriction factor, SERINC5 (Ser5), to increase viral infectivity. To explore the molecular mechanism of Ser5 antagonism by Nef, we determined how Nef affects Ser5 expression and intracellular trafficking in comparison with CD4 and MHC-I. We confirm that Nef excludes Ser5 from HIV-1 virions by downregulating its cell surface expression via similar functional motifs required for CD4-downregulation...
March 7, 2018: Journal of Virology
Hella Schmidt, Sebastian Vlaic, Thomas Krüger, Franziska Schmidt, Johannes Balkenhohl, Thomas Dandekar, Reinhard Guthke, Olaf Kniemeyer, Thorsten Heinekamp, Axel A Brakhage
Invasive infections by the human pathogenic fungus Aspergillus fumigatus start with the outgrowth of asexual, airborne spores (conidia) into the lung tissue of immunocompromised patients. The resident alveolar macrophages phagocytose conidia, which end up in phagolysosomes. However, A. fumigatus conidia resist phagocytic degradation to a certain degree. This is mainly attributable to the pigment 1,8-dihydroxynaphthalene (DHN) melanin located in the cell wall of conidia, which manipulates the phagolysosomal maturation and prevents their intracellular killing...
March 5, 2018: Molecular & Cellular Proteomics: MCP
Gati K Panigrahi, Prakash P Praharaj, Taylor C Peak, Jessica Long, Ravi Singh, Johng S Rhim, Zakaria Y Abd Elmageed, Gagan Deep
African American men in the United States have higher mortality due to prostate cancer (PCa) compared to other races. One reason for this disparity is the lack of in-depth understanding of the PCa biology in African Americans. For example, hypoxia in prostate tumor microenvironment is associated with adverse prognosis; still, no hypoxia-related studies have been reported in African Americans. Here, we compared African-American and Caucasian PCa cells for exosome secretion under normoxic (21% O2 ) and hypoxic (1% O2 ) conditions...
March 1, 2018: Scientific Reports
Ross Ferguson, Vasanta Subramanian
Angiogenin (ANG), a member of the RNase superfamily (also known as RNase 5) has neurotrophic, neuroprotective and angiogenic activities. Recently it has also been shown to be important in stem cell homeostasis. Mutations in ANG are associated with neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Fronto-temporal dementia (FTD). ANG is a secreted protein which is taken up by cells and translocated to the nucleus. However, the import pathway/s through which ANG is taken up is/are still largely unclear...
2018: PloS One
Mads Eggert Nielsen, Hans Thordal-Christensen
Plant innate immunity enables plants to defend themselves against infectious pathogens. While membrane trafficking and release of exosomes are considered vital for correct execution of innate immunity, the mechanisms behind remain elusive. Recently, we have shown that VPS9a, the general guanine-nucleotide exchange factor activating Rab5 GTPases, is required for both pre- and post-invasive immunity against powdery mildew fungi in Arabidopsis thaliana. Yet, the Arabidopsis genome contains a close homologue of VPS9a, which potentially plays specific roles in innate immunity...
February 27, 2018: Plant Signaling & Behavior
FoSheng Hsu, Stephanie Spannl, Charles Ferguson, Anthony A Hyman, Robert G Parton, Marino Zerial
Mitochondrial stress response is essential for cell survival, and damaged mitochondria are a hallmark of neurodegenerative diseases. Thus, it is fundamental to understand how mitochondria relay information within the cell. Here, by investigating mitochondrial-endosomal contact sites we made the surprising observation that the small GTPase Rab5 translocates from early endosomes to mitochondria upon oxidative stress. This process is reversible and accompanied by an increase in Rab5-positive endosomes in contact with mitochondria...
February 22, 2018: ELife
Kodai Takemoto, Kazuo Ebine, Jana Christin Askani, Falco Krüger, Zaida Andrés Gonzalez, Emi Ito, Tatsuaki Goh, Karin Schumacher, Akihiko Nakano, Takashi Ueda
Membrane trafficking plays pivotal roles in various cellular activities and higher-order functions of eukaryotes and requires tethering factors to mediate contact between transport intermediates and target membranes. Two evolutionarily conserved tethering complexes, homotypic fusion and protein sorting (HOPS) and class C core vacuole/endosome tethering (CORVET), are known to act in endosomal/vacuolar transport in yeast and animals. Both complexes share a core subcomplex consisting of Vps11, Vps18, Vps16, and Vps33, and in addition to this core, HOPS contains Vps39 and Vps41, whereas CORVET contains Vps3 and Vps8...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Naoki Minamino, Takehiko Kanazawa, Atsuko Era, Kazuo Ebine, Akihiko Nakano, Takashi Ueda
The RAB GTPase is an evolutionarily conserved machinery component of membrane trafficking, which is the fundamental system for cell viability and higher-order biological functions. The composition of RAB GTPases in each organism is closely related to the complexity and organization of the membrane-trafficking pathway, which has been developed uniquely to realize the organism-specific membrane trafficking system. Comparative genomics has suggested that terrestrialization and/or multicellularization were associated with the expansion of membrane trafficking pathways in green plants, which has yet to be validated in basal land plant lineages...
February 10, 2018: Plant & Cell Physiology
Young Kim, William A Abplanalp, Andrew D Jung, Rebecca M Schuster, Alex B Lentsch, Erich Gulbins, Charles C Caldwell, Timothy A Pritts
Microparticles are submicron vesicles shed from aging erythrocytes as a characteristic feature of the red blood cell (RBC) storage lesion. Exposure of pulmonary endothelial cells to RBC-derived microparticles promotes an inflammatory response, but the mechanisms underlying microparticle-induced endothelial cell activation are poorly understood. In the present study, cultured murine lung endothelial cells (MLECs) were treated with microparticles isolated from aged murine packed RBCs or vehicle. Microparticle-treated cells demonstrated increased expression of the adhesion molecules ICAM and E-selectin, as well as the cytokine, IL-6...
March 2018: Shock
Kate E Yu, Do-Hyoung Kim, Yong-In Kim, Walton D Jones, J Eugene Lee
Animals use their odorant receptors to receive chemical information from the environment. Insect odorant receptors differ from the G protein-coupled odorant receptors in vertebrates and nematodes, and very little is known about their protein-protein interactions. Here, we introduce a mass spectrometric platform designed for the large-scale analysis of insect odorant receptor protein-protein interactions. Using this platform, we obtained the first Orco interactome from Drosophila melanogaster. From a total of 1,186 identified proteins, we narrowed the interaction candidates to 226, of which only two-thirds have been named...
February 12, 2018: Molecules and Cells
Natalie Kofler, Federico Corti, Felix Rivera-Molina, Yong Deng, Derek Toomre, Michael Simons
As a master regulator of endothelial cell function, vascular endothelial growth factor receptor-2 (VEGFR2) activates multiple downstream signaling pathways that are critical for vascular development and normal vessel function. VEGFR2 trafficking through various endosomal compartments modulates its signaling output. Accordingly, proteins that regulate the speed and direction by which VEGFR2 traffics through endosomes have been demonstrated to be particularly important for arteriogenesis. However, little is known about how these proteins control VEGFR2 trafficking and about the implications of this control for endothelial cell function...
February 7, 2018: Journal of Biological Chemistry
Qiu-Mei Wu, Shu-Lin Liu, Gang Chen, Wei Zhang, En-Ze Sun, Geng-Fu Xiao, Zhi-Ling Zhang, Dai-Wen Pang
Autophagy is closely related to virus-induced disease and a comprehensive understanding of the autophagy-associated infection process of virus will be significant for developing more effective antiviral strategies. However, many critical issues and the underlying mechanism of autophagy in virus entry still need further investigation. Here, this study unveils the involvement of autophagy in influenza A virus entry. The quantum-dot-based single-virus tracking technique assists in real-time, prolonged, and multicolor visualization of the transport process of individual viruses and provides unambiguous dissection of the autophagic trafficking of viruses...
February 6, 2018: Small
Yingxiao Shi, Shaoyu Lin, Kim A Staats, Yichen Li, Wen-Hsuan Chang, Shu-Ting Hung, Eric Hendricks, Gabriel R Linares, Yaoming Wang, Esther Y Son, Xinmei Wen, Kassandra Kisler, Brent Wilkinson, Louise Menendez, Tohru Sugawara, Phillip Woolwine, Mickey Huang, Michael J Cowan, Brandon Ge, Nicole Koutsodendris, Kaitlin P Sandor, Jacob Komberg, Vamshidhar R Vangoor, Ketharini Senthilkumar, Valerie Hennes, Carina Seah, Amy R Nelson, Tze-Yuan Cheng, Shih-Jong J Lee, Paul R August, Jason A Chen, Nicholas Wisniewski, Victor Hanson-Smith, T Grant Belgard, Alice Zhang, Marcelo Coba, Chris Grunseich, Michael E Ward, Leonard H van den Berg, R Jeroen Pasterkamp, Davide Trotti, Berislav V Zlokovic, Justin K Ichida
An intronic GGGGCC repeat expansion in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the pathogenic mechanism of this repeat remains unclear. Using human induced motor neurons (iMNs), we found that repeat-expanded C9ORF72 was haploinsufficient in ALS. We found that C9ORF72 interacted with endosomes and was required for normal vesicle trafficking and lysosomal biogenesis in motor neurons. Repeat expansion reduced C9ORF72 expression, triggering neurodegeneration through two mechanisms: accumulation of glutamate receptors, leading to excitotoxicity, and impaired clearance of neurotoxic dipeptide repeat proteins derived from the repeat expansion...
February 5, 2018: Nature Medicine
(no author information available yet)
No abstract text is available yet for this article.
February 1, 2018: Autophagy
Nicole L Diggins, Hakmook Kang, Alissa Weaver, Donna J Webb
Cell migration is a tightly coordinated process that requires the spatiotemporal regulation of many molecular components. Because adaptor proteins can serve as integrators of cellular events, they are being increasingly studied as regulators of cell migration. The adaptor protein containing a pleckstrin-homology (PH) domain, phosphotyrosine binding (PTB) domain, and leucine zipper motif 1 (APPL1) is a 709-amino acid endosomal protein that plays a role in cell proliferation and survival as well as endosomal trafficking and signaling...
January 19, 2018: Journal of Cell Science
Koji Yamano, Chunxin Wang, Shireen A Sarraf, Christian Münch, Reika Kikuchi, Nobuo N Noda, Yohei Hizukuri, Masato T Kanemaki, Wade Harper, Keiji Tanaka, Noriyuki Matsuda, Richard J Youle
Damaged mitochondria are selectively eliminated by mitophagy. Parkin and PINK1, gene products mutated in familial Parkinson's disease, play essential roles in mitophagy through ubiquitination of mitochondria. Cargo ubiquitination by E3 ubiquitin ligase Parkin is important to trigger selective autophagy. Although autophagy receptors recruit LC3-labeled autophagic membranes onto damaged mitochondria, how other essential autophagy units such as ATG9A-integrated vesicles are recruited remains unclear. Here, using mammalian cultured cells, we demonstrate that RABGEF1, the upstream factor of the endosomal Rab GTPase cascade, is recruited to damaged mitochondria via ubiquitin binding downstream of Parkin...
January 23, 2018: ELife
Gisel S Miszczuk, Ismael R Barosso, María Cecilia Larocca, Julieta Marrone, Raúl A Marinelli, Andrea C Boaglio, Enrique J Sánchez Pozzi, Marcelo G Roma, Fernando A Crocenzi
Impaired canalicular secretion due to increased endocytosis and intracellular retention of canalicular transporters such as BSEP and MRP2 is a main, common pathomechanism of cholestasis. Nevertheless, the mechanisms governing this process are unknown. We characterized this process in estradiol 17 β-d-glucuronide (E17G)-induced cholestasis, an experimental model which partially mimics pregnancy-induced cholestasis. Inhibition of clathrin-mediated endocytosis (CME) with monodansylcadaverine (MDC) or K+ depletion, but not the caveolin-mediated endocytosis inhibitors filipin and genistein, prevented E17G-induced endocytosis of BSEP and MRP2, and the associated impairment of activity of these transporters in isolated rat hepatocyte couplets (IRHC)...
January 17, 2018: Biochimica et Biophysica Acta
Mike Gerards, Giuseppe Cannino, Jose M González de Cózar, Howard T Jacobs
The Drosophila gene products Bet1, Slh and CG10144, predicted to function in intracellular vesicle trafficking, were previously found to be essential for mitochondrial nucleoid maintenance. Here we show that Slh and Bet1 co-operate to maintain mitochondrial functions. In their absence, mitochondrial content, membrane potential and respiration became abnormal, accompanied by mitochondrial proteotoxic stress, but without direct effects on mtDNA. Immunocytochemistry showed that both Slh and Bet1 are localized at the Golgi, together with a proportion of Rab5-positive vesicles...
January 17, 2018: Molecular Biology of the Cell
Mary M Weber, Robert Faris, Erin J van Schaik, James E Samuel
Coxiella burnetii is an obligate intracellular pathogen that replicates in an endolysosome-like compartment termed the Coxiella-containing vacuole (CCV). Formation of this unique replicative niche requires delivery of bacterial effector proteins into the host cytosol where they mediate crucial interactions with the host. We previously identified an essential Dot/Icm effector, CirA that is required for intracellular replication and CCV formation. Furthermore, CirA was shown to stimulate the GTPase activity of RhoA in vitro...
January 10, 2018: Microbes and Infection
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