journal
MENU ▼
Read by QxMD icon Read
search

Molecular Biology of the Cell

journal
https://www.readbyqxmd.com/read/29668363/a-data-entrained-computational-model-for-testing-the-regulatory-logic-of-the-vertebrate-unfolded-protein-response
#1
Danilo R Diedrichs, Javier A Gomez, Chun-Sing Huang, D Thomas Rutkowski, Rodica Curtu
The vertebrate unfolded protein response (UPR) is characterized by multiple interacting nodes among its three pathways, yet the logic underlying this regulatory complexity is unclear. To begin to address this issue, we created a computational model of the vertebrate UPR that was entrained upon and then validated against experimental data. As part of this validation, the model successfully predicted the phenotypes of cells with lesions in UPR signaling, including a surprising and previously unreported differential role for the eIF2α phosphatase GADD34 in exacerbating severe stress but ameliorating mild stress...
April 18, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29668357/formin-dependent-tgf-%C3%AE-signaling-for-epithelial-to-mesenchymal-transition
#2
Manish K Rana, Francesca M Aloisio, Changhoon Choi, Diane L Barber
The role of distinct actin filaments architectures in epithelial plasticity remains incompletely understood. We, therefore, determined roles for formins and the Arp2/3 complex, which are actin nucleators generating unbranched and branched actin filaments, respectively, in the process of epithelial to mesenchymal transition (EMT). In clonal lung, mammary and renal epithelial cells, the formin activity inhibitor SMIFH2 but not the Arp2/3 complex activity inhibitor CK666 blocked EMT induced by TGF-β. SMIFH2 prevented the proximal signal of increased Smad2 phosphorylation, and hence also blocked downstream EMT markers, including actin filament remodeling, decreased expression of the adherens junction protein E-cadherin and increased expression of the matrix protein fibronectin and the transcription factor Snail...
April 18, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29668350/the-tomosyn-homolog-sro7-is-a-direct-effector-of-the-rab-gtpase-sec4-in-post-golgi-vesicle-tethering
#3
Guendalina Rossi, Kelly Watson, Wade Kennedy, Patrick Brennwald
The tomosyn/Sro7 family is thought to play an important role in cell surface trafficking both as an effector of Rab family GTPases and as a regulator of plasma membrane SNARE function. Recent work has determined the binding site of GTP-bound Sec4 on Sro7. Here we examine the effect of mutations in Sro7 that block Sec4 binding to determine the role of this interaction in Sro7 function. Using an in vitro vesicle:vesicle tethering assay, we find that most of Sro7's ability to tether vesicles is blocked by mutations that disrupt binding to Sec4-GTP...
April 18, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29668348/phosphatidylserine-and-gtpase-activation-control-cdc42-nanoclustering-to-counter-dissipative-diffusion
#4
Elodie Sartorel, Caner Ünlü, Mini Jose, Aurélie Massoni-Laporte, Julien Meca, Jean-Baptiste Sibarita, Derek McCusker
The anisotropic organization of plasma membrane constituents is indicative of mechanisms that drive the membrane away from equilibrium. However, defining these mechanisms is challenging due to the short spatio-temporal scales at which diffusion operates. Here, we use high-density single protein tracking combined with photoactivation localization microscopy (sptPALM) to monitor Cdc42 in budding yeast, a system in which Cdc42 exhibits anisotropic organization. Cdc42 exhibited reduced mobility at the cell pole, where it was organized in nanoclusters...
April 18, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29563255/reciprocal-regulation-of-enos-and-caveolin-1-functions-in-endothelial-cells
#5
Zhenlong Chen, Suellen D'Arc Oliveira, Adriana M Zimnicka, Ying Jiang, Tiffany Sharma, Stone Chen, Orly Lazarov, Marcelo G Bonini, Jacob M Haus, Richard D Minshall
We hypothesized that the maintenance of vascular homeostasis is critically dependent on the expression and reciprocal regulation of caveolin-1 (Cav-1) and endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs). Skeletal muscle biopsies from subjects with type II diabetes showed 50% less Cav-1 and eNOS compared to lean healthy controls. The Cav-1:eNOS expression ratio was 200:1 in primary culture human ECs. Cav-1 siRNA reduced eNOS protein and gene expression in association with a 2-fold increase in eNOS phosphorylation and nitrate production per molecule of eNOS which was reversed in cells overexpressing Adv-Cav-1-GFP...
March 21, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29563254/phosphorylation-of-mcad-selectively-rescues-pink1-deficiencies-in-behavior-and-metabolism
#6
Meredith M Course, Anna I Scott, Carmen Schoor, Chung-Han Hsieh, Amanda M Papakyrikos, Dominic Winter, Tina M Cowan, Xinnan Wang
PINK1 is a mitochondria-targeted kinase, whose mutations are a cause of Parkinson's disease. We set out to better understand PINK1's effects on mitochondrial proteins in vivo Using an unbiased phosphoproteomic screen in Drosophila , we found that PINK1 mediates the phosphorylation of MCAD, a mitochondrial matrix protein critical to fatty acid metabolism. By mimicking phosphorylation of this protein in a PINK1 null background, we restored PINK1 null's climbing, flight, thorax, and wing deficiencies. Due to MCAD's role in fatty acid metabolism, we examined the metabolic profile of PINK1 null flies, where we uncovered significant disruptions in both acylcarnitines and amino acids...
March 21, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29540532/mapping-the-mammalian-ribosome-quality-control-complex-interactome-using-proximity-labeling-approaches
#7
Nathan Zuzow, Arit Ghosh, Marilyn Leonard, Jeffrey Liao, Bing Yang, Eric J Bennett
Previous genetic and biochemical studies from S. cerevisiae have identified a critical ribosome-associated quality control complex (RQC) that facilitates resolution of stalled ribosomal complexes. While components of the mammalian RQC have been examined in vitro , a systematic characterization of RQC protein interactions in mammalian cells has yet to be described. Here, we utilize both proximity-labeling proteomic approaches, BioID and APEX, and traditional affinity-based strategies to both identify interacting proteins of mammalian RQC members and putative substrates for the RQC resident E3 ligase, Ltn1...
March 14, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29540531/intraflagellar-transport-is-deeply-integrated-in-hedgehog-signaling
#8
Thibaut Eguether, Fabrice P Cordelieres, Gregory J Pazour
The vertebrate hedgehog pathway is organized in primary cilia and hedgehog components relocate into or out of cilia during signaling. Defects in intraflagellar transport (IFT) typically disrupt ciliary assembly and attenuate hedgehog signaling. Determining if IFT drives the movement of hedgehog components is difficult due to the requirement of IFT for building cilia. Unlike most IFT proteins, IFT27 is dispensable for cilia formation but affects hedgehog signaling similar to other IFTs allowing us to examine its role in the dynamics of signaling...
March 14, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29540530/control-of-insulin-granule-formation-and-function-by-the-abc-transporters-abcg1-and-abca1-and-by-oxysterol-binding-protein-osbp
#9
Syed Saad Hussain, Megan T Harris, Alex J B Kreutzberger, Candice M Inouye, Catherine A Doyle, Anna M Castle, Peter Arvan, J David Castle
In pancreatic β cells, insulin granule membranes are enriched in cholesterol and are both recycled and newly generated. Cholesterol's role in supporting granule membrane formation and function is poorly understood.<u>A</u>TP<u>b</u>inding<u>c</u>assette transporters ABCG1 and ABCA1 regulate intracellular cholesterol and are important for insulin secretion. RNAi-induced depletion in cultured pancreatic β cells shows that ABCG1 is needed to stabilize newly made insulin granules against lysosomal degradation; ABCA1 is also involved but to a lesser extent...
March 14, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29540529/the-dynamic-atg13-free-conformation-of-the-atg1-eat-domain-is-required-for-phagophore-expansion
#10
Mary G Lin, Johannes Schöneberg, Christopher W Davies, Xuefeng Ren, James H Hurley
Yeast macroautophagy begins with the de novo formation of a double membrane phagophore at the preautophagosomal structure (PAS), followed by its expansion into the autophagosome responsible for cargo engulfment. The kinase Atg1 is recruited to the PAS by Atg13 through interactions between the EAT domain of the former and the tMIM motif of the latter. Mass spectrometry data has shown that in the absence of Atg13, the EAT domain structure is strikingly dynamic, but the function of this Atg13-free dynamic state has been unclear...
March 14, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29540528/phospholipid-flippases-and-sfk1p-a-novel-regulator-of-phospholipid-asymmetry-contribute-to-low-permeability-of-the-plasma-membrane
#11
Tetsuo Mioka, Konomi Fujimura-Kamada, Nahiro Mizugaki, Takuma Kishimoto, Takamitsu Sano, Hitoshi Nunome, David E Williams, Raymond J Andersen, Kazuma Tanaka
Phospholipid flippase (type 4 P-type ATPase) plays a major role in the generation of phospholipid asymmetry in eukaryotic cell membranes. Loss of Lem3p-Dnf1/2p flippases leads to the exposure of phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the cell surface in yeast, resulting in sensitivity to PS- or PE-binding peptides. We isolated Sfk1p, a conserved membrane protein in the TMEM150/FRAG1/DRAM family, as a multicopy suppressor of this sensitivity. Overexpression of SFK1 decreased PS/PE exposure in lem3 Δ mutant cells...
March 14, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29540527/a-biosensor-for-mapk-dependent-lin28-signaling
#12
Laurel M Oldach, Kirill Gorshkov, William T Mills, Jin Zhang, Mollie K Meffert
Intracellular levels of the RNA-binding protein and pluripotency factor, Lin28a, are tightly controlled to govern cellular and organismal growth. Lin28a is extensively regulated at the post-transcriptional level, and can undergo mitogen-activated protein kinase (MAPK)-mediated elevation from low basal levels in differentiated cells by phosphorylation-dependent stabilizing interaction with the RNA-silencing factor HIV TAR-RNA-binding protein (TRBP). However, molecular and spatio-temporal details of this critical control mechanism remained unknown...
March 14, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29540526/human-clasp2-specifically-regulates-microtubule-catastrophe-and-rescue
#13
Elizabeth J Lawrence, Göker Arpağ, Stephen R Norris, Marija Zanic
Cytoplasmic Linker-Associated Proteins (CLASPs) are microtubule-associated proteins essential for microtubule regulation in many cellular processes. However, the molecular mechanisms underlying CLASP activity are not understood. Here, we use purified protein components and Total Internal Reflection Fluorescence (TIRF) microscopy to investigate the effects of human CLASP2 on microtubule dynamics in vitro We demonstrate that CLASP2 suppresses microtubule catastrophe and promotes rescue without affecting the rates of microtubule growth or shrinkage...
March 14, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29540525/a-microtubule-dynein-tethering-complex-regulates-the-axonemal-inner-dynein-f-i1
#14
Tomohiro Kubo, Yuqing Hou, Deborah A Cochran, George B Witman, Toshiyuki Oda
Motility of cilia/flagella is generated by a coordinated activity of thousands of dyneins. Inner dynein arms (IDAs) are particularly important for the formation of ciliary/flagellar waveforms, but the molecular mechanism of IDA regulation is poorly understood. Here, we show using cryo-electron tomography and biochemical analyses of Chlamydomonas flagella that a conserved protein FAP44 forms a complex that tethers IDA f (I1 dynein) head domains to the A-tubule of the axonemal outer doublet microtubule. In wild-type flagella, IDA f showed little nucleotide-dependent movement except for a tilt in the f β head perpendicular to the microtubule-sliding direction...
March 14, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29514933/the-yeast-arrestin-related-protein-bul1-is-a-novel-actor-of-glucose-induced-endocytosis
#15
Junie Hovsepian, Véronique Albanèse, Michel Becuwe, Vasyl Ivashov, David Teis, Sébastien Léon
Yeast cells have a remarkable ability to adapt to nutritional changes in their environment. During adaptation, nutrient-signalling pathways drive the selective endocytosis of nutrient transporters present at the cell surface. A current challenge is to understand the mechanistic basis of this regulation. Transporter endocytosis is triggered by their ubiquitylation, which involves the ubiquitin ligase Rsp5 and its adaptors of the arrestin-related family (ART). This step is highly regulated by nutrient availability...
March 7, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29514932/a-newly-characterized-vacuolar-serine-carboxypeptidase-atg42-ybr139w-is-required-for-normal-vacuole-function-and-the-terminal-steps-of-autophagy-in-the-yeast-saccharomyces-cerevisiae
#16
Katherine R Parzych, Aileen Ariosa, Muriel Mari, Daniel J Klionsky
Macroautophagy (hereafter autophagy) is a cellular recycling pathway essential for cell survival during nutrient deprivation that culminates in the degradation of cargo within the vacuole in yeast and the lysosome in mammals, followed by efflux of the resultant macromolecules back into the cytosol. The yeast vacuole is home to many different hydrolytic proteins and while few have established roles in autophagy, the involvement of others remains unclear. The vacuolar serine carboxypeptidase Prc1 (carboxypeptidase Y) has not been previously shown to have a role in vacuolar zymogen activation and has not been directly implicated in the terminal degradation steps of autophagy...
March 7, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29514931/voltage-gated-potassium-channel-blocker-4-aminopyridine-induces-glioma-cell-apoptosis-by-reducing-expression-of-microrna-10b-5p
#17
Qin Ru, Wei-Ling Li, Qi Xiong, Lin Chen, Xiang Tian, Chao-Ying Li
Accumulating evidence has demonstrated that voltage-gated potassium channels (Kv channels) were associated with regulating cell proliferation and apoptosis in tumor cells. Our previous study proved that Kv channel blocker, 4-aminopyridine (4-AP) could inhibit cell proliferation and induce apoptosis in glioma. However, the precise mechanisms were not clear yet. MicroRNAs (miRNAs) are small non-coding RNAs that act as key mediators in the progression of tumor, so the aim of this study was to investigate the role of miRNAs in the apoptosis-promoting effect of 4-AP in glioma cells...
March 7, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29514930/inositol-polyphosphate-multikinase-regulation-of-trypanosoma-brucei-life-stage-development
#18
Igor Cestari, Atashi Anupama, Kenneth Stuart
Many cellular processes change during the Trypanosoma brucei life cycle as this parasite alternates between the mammalian host and tsetse fly vector. We show that the inositol phosphate pathway helps regulate these developmental changes. Knockdown of inositol polyphosphate multikinase (IPMK), which phosphorylates Ins(1,4,5)P3 and Ins(1,3,4,5)P4, resulted in changes in bloodstream forms that are characteristic of insect stage procyclic forms. These changes include expression of the procyclic surface coat, upregulation of RNA-binding proteins that we show to regulate stage-specific transcripts, and activation of oxidative phosphorylation with increased ATP production in bloodstream forms...
March 7, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29514929/fluorescence-fluctuation-spectroscopy-reveals-differential-sun-protein-oligomerization-in-living-cells
#19
Jared Hennen, Cosmo A Saunders, Joachim D Mueller, G W Gant Luxton
Linker of nucleoskeleton and cytoskeleton (LINC) complexes are conserved molecular bridges within the nuclear envelope that mediate mechanical force transmission into the nucleoplasm. The core of the LINC complex is formed by a transluminal interaction between the outer and inner nuclear membrane KASH and SUN proteins, respectively. Mammals encode six KASH proteins and five SUN proteins. Recently, KASH proteins were shown to bind to the domain interfaces of trimeric SUN2 proteins in vitro However neither the existence of SUN2 trimers in living cells nor the extent to which other SUN proteins conform to this assembly state have been tested experimentally...
March 7, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29514928/the-i1-dynein-associated-tether-and-tether-head-complex-is-a-conserved-regulator-of-ciliary-motility
#20
Gang Fu, Qian Wang, Nhan Phan, Paulina Urbanska, Ewa Joachimiak, Jianfeng Lin, Dorota Wloga, Daniela Nicastro
Motile cilia are essential for propelling cells and moving fluids across tissues. The activity of axonemal dynein motors must be precisely coordinated to generate ciliary motility, but their regulatory mechanisms are not well understood. The tether and tether head (T/TH) complex was hypothesized to provide mechanical feedback during ciliary beating because it links the motor domains of the regulatory I1 dynein to the ciliary doublet microtubule. Combining genetic and biochemical approaches with cryo-electron tomography, we identified FAP44 and FAP43 (plus the algae-specific, FAP43-redundant FAP244) as T/TH components...
March 7, 2018: Molecular Biology of the Cell
journal
journal
30926
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"