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https://www.readbyqxmd.com/read/27910904/melanosome-transfer-to-keratinocyte-in-the-chicken-embryonic-skin-is-mediated-by-vesicle-release-associated-with-rho-regulated-membrane-blebbing
#1
Ryosuke Tadokoro, Hidetaka Murai, Ken-Ichiro Sakai, Takahiro Okui, Yasuhiro Yokota, Yoshiko Takahashi
During skin pigmentation in amniotes, melanin synthesized in the melanocyte is transferred to keratinocytes by a particle called the melanosome. Previous studies, mostly using dissociated cultured cells, have proposed several different models that explain how the melanosome transfer is achieved. Here, using a technique that labels the plasma membrane of melanocytes within a three-dimensional system that mimics natural tissues, we have visualized the plasma membrane of melanocytes with EGFP in chicken embryonic skin...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27907123/mice-hemizygous-for-a-pathogenic-mitofusin-2-allele-exhibit-hind-limb-foot-gait-deficits-and-phenotypic-perturbations-in-nerve-and-muscle
#2
Peter Bannerman, Travis Burns, Jie Xu, Laird Miers, David Pleasure
Charcot-Marie-Tooth disease type 2A (CMT2A), the most common axonal form of hereditary sensory motor neuropathy, is caused by mutations of mitofusin-2 (MFN2). Mitofusin-2 is a GTPase required for fusion of mitochondrial outer membranes, repair of damaged mitochondria, efficient mitochondrial energetics, regulation of mitochondrial-endoplasmic reticulum calcium coupling and axonal transport of mitochondria. We knocked T105M MFN2 preceded by a loxP-flanked STOP sequence into the mouse Rosa26 locus to permit cell type-specific expression of this pathogenic allele...
2016: PloS One
https://www.readbyqxmd.com/read/27902969/rac1-gtp-ase-signals-wnt-beta-catenin-pathway-mediated-integrin-directed-metastasis-associated-tumor-cell-phenotypes-in-triple-negative-breast-cancers
#3
Pradip De, Jennifer H Carlson, Tyler Jepperson, Scooter Willis, Brian Leyland-Jones, Nandini Dey
The acquisition of integrin-directed metastasis-associated (ID-MA) phenotypes by Triple-Negative Breast Cancer (TNBC) cells is caused by an upregulation of the Wnt-beta-catenin pathway (WP). We reported that WP is one of the salient genetic features of TNBC. RAC-GTPases, small G-proteins which transduce signals from cell surface proteins including integrins, have been implicated in tumorigenesis and metastasis by their role in essential cellular functions like motility. The collective percentage of alteration(s) in RAC1 in ER+ve BC was lower as compared to ER-ve BC (35% vs 57%) (brca/tcga/pub2015)...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901125/rab14-specifies-the-apical-membrane-through-arf6-mediated-regulation-of-lipid-domains-and-cdc42
#4
Ruifeng Lu, Jean M Wilson
The generation of cell polarity is essential for the development of multi-cellular organisms as well as for the function of epithelial organs in the mature animal. Small GTPases regulate the establishment and maintenance of polarity through effects on cytoskeleton, membrane trafficking, and signaling. Using short-term 3-dimensional culture of MDCK cells, we find that the small GTPase Rab14 is required for apical membrane specification. Rab14 knockdown results in disruption of polarized lipid domains and failure of the Par/aPKC/Cdc42 polarity complex to localize to the apical membrane...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900004/role-of-specific-dna-mutations-in-the-peripheral-blood-of-colorectal-cancer-patients-for-the-assessment-of-tumor-stage-and-residual-disease-following-tumor-resection
#5
Gregor Norcic, Franc Jelenc, Petra Cerkovnik, Vida Stegel, Srdjan Novakovic
In the present study, the detection of tumor-specific KRAS proto-oncogene, GTPase (KRAS) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations in the peripheral blood of colorectal cancer (CRC) patients at all stages and adenomas was used for the estimation of disease stage prior to surgery and for residual disease following surgery. A total of 65 CRC patients were enrolled. The primary tumor tested positive for the specific mutations (KRAS mutations in codons 12, 13, 61, 117 or 146 and BRAF mutations in codon 600) in 35 patients...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899881/transcriptomics-of-environmental-enrichment-reveals-a-role-for-retinoic-acid-signaling-in-addiction
#6
Yafang Zhang, Fanping Kong, Elizabeth J Crofton, Steven N Dragosljvich, Mala Sinha, Dingge Li, Xiuzhen Fan, Shyny Koshy, Jonathan D Hommel, Heidi M Spratt, Bruce A Luxon, Thomas A Green
There exists much variability in susceptibility/resilience to addiction in humans. The environmental enrichment paradigm is a rat model of resilience to addiction-like behavior, and understanding the molecular mechanisms underlying this protective phenotype may lead to novel targets for pharmacotherapeutics to treat cocaine addiction. We investigated the differential regulation of transcript levels using RNA sequencing of the rat nucleus accumbens after environmental enrichment/isolation and cocaine/saline self-administration...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27899316/inhibition-or-ablation-of-transglutaminase-2-impairs-astrocyte-migration
#7
Alina Monteagudo, Changyi Ji, Abdullah Akbar, Jeffrey W Keillor, Gail V W Johnson
Astrocytes play numerous complex roles that support and facilitate the function of neurons. Further, when there is an injury to the central nervous system (CNS) they can both facilitate or ameliorate functional recovery depending on the location and severity of the injury. When a CNS injury is relatively severe a glial scar is formed, which is primarily composed of astrocytes. The glial scar can be both beneficial, by limiting inflammation, and detrimental, by preventing neuronal projections, to functional recovery...
November 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27898700/sbg1-is-a-novel-regulator-for-the-localization-of-the-%C3%AE-glucan-synthase-bgs1-in-fission-yeast
#8
Reshma Davidson, Josef A Pontasch, Jian-Qiu Wu
Glucan synthases synthesize glucans, complex polysaccharides that are the major components in fungal cell walls and division septa. Studying regulation of glucan synthases is important as they are essential for fungal cell survival and thus popular targets for anti-fungal drugs. Linear 1,3-β-glucan is the main component of primary septum and is synthesized by the conserved β-glucan synthase Bgs1 in fission yeast cytokinesis. It is known that Rho1 GTPase regulates Bgs1 catalytic activity and the F-BAR protein Cdc15 plays a role in Bgs1 delivery to the plasma membrane...
2016: PloS One
https://www.readbyqxmd.com/read/27898263/genetic-alterations-affecting-gtpases-and-t-cell-receptor-signaling-in-peripheral-t-cell-lymphomas
#9
Rebecca L Boddicker, Gina L Razidlo, Andrew L Feldman
Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy...
November 29, 2016: Small GTPases
https://www.readbyqxmd.com/read/27897225/calmodulin-interacts-with-rab3d-and-modulates-osteoclastic-bone-resorption
#10
Sipin Zhu, Shek Man Chim, Taksum Cheng, Estabelle Ang, Benjamin Ng, Baysie Lim, Kai Chen, Heng Qiu, Jennifer Tickner, Huazi Xu, Nathan Pavlos, Jiake Xu
Calmodulin is a highly versatile protein that regulates intracellular calcium homeostasis and is involved in a variety of cellular functions including cardiac excitability, synaptic plasticity and signaling transduction. During osteoclastic bone resorption, calmodulin has been reported to concentrate at the ruffled border membrane of osteoclasts where it is thought to modulate bone resorption activity in response to calcium. Here we report an interaction between calmodulin and Rab3D, a small exocytic GTPase and established regulator osteoclastic bone resorption...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895118/co-evolution-of-two-gtpases-enables-efficient-protein-targeting-in-an-rna-less-chloroplast-signal-recognition-particle-pathway
#11
Sowmya Chandrasekar, Michael J Sweredoski, Chang Ho Sohn, Sonja Hess, Shu-Ou Shan
Signal Recognition Particle (SRP) is an essential ribonucleoprotein particle that mediates the co-translational targeting of newly synthesized proteins to cellular membranes. The SRP RNA is a universally conserved component of SRP that mediates key interactions between two GTPases in SRP and its receptor, and thus enables rapid delivery of cargo to the target membrane. Notably, this essential RNA is bypassed in the chloroplast SRP (cpSRP) of green plants. Previously, we showed that the cpSRP and cpSRP receptor GTPases (cpSRP54 and cpFtsY, respectively) could interact efficiently by themselves without the SRP RNA...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27894934/mir-142-is-required-for-staphylococcus-aureus-clearance-at-skin-wound-sites-via-small-gtpase-mediated-regulation-of-the-neutrophil-actin-cytoskeleton
#12
Katsuya Tanaka, Sang Eun Kim, Hiroki Yano, Gaku Matsumoto, Ryoma Ohuchida, Yuhoko Ishikura, Masatake Araki, Kimi Araki, Seongjoon Park, Toshimitsu Komatsu, Hiroko Hayashi, Kazuya Ikematsu, Katsumi Tanaka, Akiyoshi Hirano, Paul Martin, Isao Shimokawa, Ryoichi Mori
MicroRNAs (miRNAs) are small noncoding RNAs that regulate protein translation by binding to complementary target mRNAs. We previously identified two mature members of the miR-142 family, miR-142-5p and miR-142-3p, as inflammation-related miRNAs with potential roles in wound healing. Here, we demonstrated that these two miRNAs are prominently expressed in wound-infiltrated neutrophils and macrophages and play central roles in wound healing. We generated miR-142(-/-) mice using the exchangeable gene-trap method and showed that healing of Staphylococcus aureus-infected skin wounds was significantly delayed in miR-142(-/-) mice compared with that in wild-type mice...
November 25, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27894104/proteomic-profiling-of-nci-60-extracellular-vesicles-uncovers-common-protein-cargo-and-cancer-type-specific-biomarkers
#13
Stephanie N Hurwitz, Mark A Rider, Joseph L Bundy, Xia Liu, Rakesh K Singh, David G Meckes
Packed with biological information, extracellular vesicles (EVs) offer exciting promise for biomarker discovery and applications in therapeutics and non-invasive diagnostics. Currently, our understanding of EV contents is confined by the limited cells from which vesicles have been characterized utilizing the same enrichment method. Using sixty cell lines from the National Cancer Institute (NCI-60), here we provide the largest proteomic profile of EVs in a single study, identifying 6,071 proteins with 213 common to all isolates...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893804/tgfbeta-induces-binucleation-polyploidization-in-hepatocytes-through-a-src-dependent-cytokinesis-failure
#14
Marco De Santis Puzzonia, Angela Maria Cozzolino, Germana Grassi, Francesca Bisceglia, Raffaele Strippoli, Giulia Guarguaglini, Franca Citarella, Benedetto Sacchetti, Marco Tripodi, Alessandra Marchetti, Laura Amicone
In all mammals, the adult liver shows binucleated as well as mononucleated polyploid hepatocytes. The hepatic polyploidization starts after birth with an extensive hepatocyte binucleation and generates hepatocytes of several ploidy classes. While the functional significance of hepatocyte polyploidy is becoming clearer, how it is triggered and maintained needs to be clarified. Aim of this study was to identify a major inducer of hepatocyte binucleation/polyploidization and the cellular and molecular mechanisms involved...
2016: PloS One
https://www.readbyqxmd.com/read/27892645/endothelial-cell-derived-endothelin-1-is-involved-in-abnormal-scar-formation-by-dermal-fibroblasts-through-rhoa-rho-kinase-pathway
#15
Koichiro Kiya, Tateki Kubo, Kenichiro Kawai, Shinsuke Matsuzaki, Rieko Muramatsu, Daisuke Maeda, Toshihiro Fujiwara, Akimitsu Nishibayashi, Shigeyuki Kanazawa, Kenji Yano, Genki Amano, Taiichi Katayama, Ko Hosokawa
Hypertrophic scars and keloids are characterized by excessive dermal deposition of extracellular matrix due to fibroblast-to-myofibroblast differentiation. Endothelin-1 (ET-1) is primarily produced by vascular endothelial cells, and plays multiple roles in the wound-healing response and organ fibrogenesis. In this study, we investigated the pathophysiological significance of ET-1 and involvement of RhoA, a member of the Rho GTPases, in hypertrophic scar/keloid formation. We found that ET-1 expression on dermal microvascular endothelial cells (ECs) in hypertrophic scars and keloids was higher than that in normal skin and mature scars...
November 28, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27891552/enteric-glial-cells-are-susceptible-to-clostridium-difficile-toxin-b
#16
Katia Fettucciari, Pamela Ponsini, Davide Gioè, Lara Macchioni, Camilla Palumbo, Elisabetta Antonelli, Stefano Coaccioli, Vincenzo Villanacci, Lanfranco Corazzi, Pierfrancesco Marconi, Gabrio Bassotti
Clostridium difficile causes nosocomial/antibiotic-associated diarrhoea and pseudomembranous colitis. The major virulence factors are toxin A and toxin B (TcdB), which inactivate GTPases by monoglucosylation, leading to cytopathic (cytoskeleton alteration, cell rounding) and cytotoxic effects (cell-cycle arrest, apoptosis). C. difficile toxins breaching the intestinal epithelial barrier can act on underlying cells, enterocytes, colonocytes, and enteric neurons, as described in vitro and in vivo, but until now no data have been available on enteric glial cell (EGC) susceptibility...
November 28, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27890731/mechanisms-of-cdc42-mediated-rat-msc-differentiation-on-micro-nano-textured-topography
#17
Guangwen Li, Yanyan Song, Mengqi Shi, Yuanhong Du, Wei Wang, Yumei Zhang
Micro/nano-textured titanium surface topography promotes osteoblast differentiation and the Wnt/β-catenin signaling pathway. However, the response of rat bone mesenchymal stem cells (MSCs) to micro/nano-textured topography, and the underlying mechanisms of its effects, are not well understood. We hypothesized that cell division cycle 42 protein (Cdc42), a key member of the Rho GTPases family, may regulate rat MSCs morphology and osteogenic differentiation by micro/nano-textured topography, and that crosstalk between Cdc42 and Wnt/ β -catenin is the underlying mechanism...
November 24, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27888137/the-role-of-rhoa-in-retrograde-neuronal-death-and-axon-regeneration-after-spinal-cord-injury
#18
Jianli Hu, Guixin Zhang, William Rodemer, Li-Qing Jin, Michael Shifman, Michael E Selzer
Paralysis following spinal cord injury (SCI) is due to interruption of axons and their failure to regenerate. It has been suggested that the small GTPase RhoA may be an intracellular signaling convergence point for several types of growth-inhibiting extracellular molecules. Even if this is true in vitro, it is not clear from studies in mammalian SCI, whether the effects of RhoA manipulations on axon growth in vivo are due to a RhoA-mediated inhibition of true regeneration or only of collateral sprouting from spared axons, since work on SCI generally is performed with partial injury models...
November 22, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27888097/rab7a-regulates-cell-migration-through-rac1-and-vimentin
#19
Azzurra Margiotta, Cinzia Progida, Oddmund Bakke, Cecilia Bucci
Rab7a, a small GTPase of the Rab family, is localized to late endosomes and controls late endocytic trafficking. The discovery of several Rab7a interacting proteins revealed that Rab7a function is closely connected to cytoskeletal elements. Indeed, Rab7a recruits on vesicles RILP and FYCO that are responsible for the movement of Rab7a-positive vesicles and/or organelles on microtubule tracks, but also directly interacts with Rac1, a fundamental regulator of actin cytoskeleton, and with peripherin and vimentin, two intermediate filament proteins...
November 22, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27886395/popdc1-bves-functions-in-the-preservation-of-cardiomyocyte-viability-while-affecting-rac1-activity-and-bnip3-expression
#20
Kliminski Vitaly, Uziel Orit, Kessler-Icekson Gania
The Popeye domain containing1, also called Bves (Popdc1/Bves), is a transmembrane protein that functions in muscle regeneration, heart rate regulation, hypoxia tolerance, and ischemia preconditioning. The expression of Popdc1/Bves is elevated in cardiomyocytes maintained in serum free defined medium. We hypothesized that Popdc1/Bves is important for cardiomyocyte survival under the stress of serum deprivation and investigated the mechanisms involved. A deficit in Popdc1/Bves, achieved by siRNA-mediated gene silencing, results in cardiomyocyte injury and death, upregulation of the pro-apoptotic protein Bcl-2/adenovirus E1B 19-kDa interacting protein3 (Bnip3), as well as reduction in Rac1-GTPase activity and in Akt phosphorylation...
November 25, 2016: Journal of Cellular Biochemistry
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