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https://www.readbyqxmd.com/read/28937994/modeling-of-annexin-a2-membrane-interactions-by-molecular-dynamics-simulations
#1
Davit Hakobyan, Volker Gerke, Andreas Heuer
The annexins are a family of Ca2+-regulated phospholipid binding proteins that are involved in membrane domain organization and membrane trafficking. Although they are widely studied and crystal structures are available for several soluble annexins their mode of membrane association has never been studied at the molecular level. Here we obtained molecular information on the annexin-membrane interaction that could serve as paradigm for the peripheral membrane association of cytosolic proteins by Molecular Dynamics simulations...
2017: PloS One
https://www.readbyqxmd.com/read/28936784/cryo-em-structures-of-the-mammalian-endo-lysosomal-trpml1-channel-elucidate-the-combined-regulation-mechanism
#2
Sensen Zhang, Ningning Li, Wenwen Zeng, Ning Gao, Maojun Yang
TRPML1 channel is a non-selective group-2 transient receptor potential (TRP) channel with Ca(2+) permeability. Located mainly in late endosome and lysosome of all mammalian cell types, TRPML1 is indispensable in the processes of endocytosis, membrane trafficking, and lysosome biogenesis. Mutations of TRPML1 cause a severe lysosomal storage disorder called mucolipidosis type IV (MLIV). In the present study, we determined the cryo-electron microscopy (cryo-EM) structures of Mus musculus TRPML1 (mTRPML1) in lipid nanodiscs and Amphipols...
September 21, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28934248/vps35-deficiency-impairs-slc4a11-trafficking-and-promotes-corneal-dystrophy
#3
Wei Liu, Fu-Lei Tang, Sen Lin, Kai Zhao, Lin Mei, Jian Ye, Wen-Cheng Xiong
Vps35 (vacuolar protein sorting 35) is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins. Dysfunction of retromer is a risk factor for the pathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD). However, Vps35/retromer's function in the eye or the contribution of Vps35-deficiency to eye degenerative disorders remains to be explored. Here we provide evidence for a critical role of Vps35 in mouse corneal dystrophy. Vps35 is expressed in mouse and human cornea...
2017: PloS One
https://www.readbyqxmd.com/read/28934222/endogenous-rgs14-is-a-cytoplasmic-nuclear-shuttling-protein-that-localizes-to-juxtanuclear-membranes-and-chromatin-rich-regions-of-the-nucleus
#4
Mary Rose Branch, John R Hepler
Regulator of G protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates G protein and H-Ras/MAPkinase signaling pathways to regulate synaptic plasticity important for hippocampal learning and memory. However, to date, little is known about the subcellular distribution and roles of endogenous RGS14 in a neuronal cell line. Most of what is known about RGS14 cellular behavior is based on studies of tagged, recombinant RGS14 ectopically overexpressed in unnatural host cells. Here, we report for the first time a comprehensive assessment of the subcellular distribution and dynamic localization of endogenous RGS14 in rat B35 neuroblastoma cells...
2017: PloS One
https://www.readbyqxmd.com/read/28934205/a-rab5-gtpase-module-is-important-for-autophagosome
#5
Fan Zhou, Shenshen Zou, Yong Chen, Zhanna Lipatova, Dan Sun, Xiaolong Zhu, Rui Li, Zulin Wu, Weiming You, Xiaoxia Cong, Yiting Zhou, Zhiping Xie, Valeriya Gyurkovska, Yutao Liu, Qunli Li, Wenjing Li, Jie Cheng, Yongheng Liang, Nava Segev
In the conserved autophagy pathway, the double-membrane autophagosome (AP) engulfs cellular components to be delivered for degradation in the lysosome. While only sealed AP can productively fuse with the lysosome, the molecular mechanism of AP closure is currently unknown. Rab GTPases, which regulate all intracellular trafficking pathways in eukaryotes, also regulate autophagy. Rabs function in GTPase modules together with their activators and downstream effectors. In yeast, an autophagy-specific Ypt1 GTPase module, together with a set of autophagy-related proteins (Atgs) and a phosphatidylinositol-3-phosphate (PI3P) kinase, regulates AP formation...
September 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28933649/legionella-blocks-autophagy-by-cleaving-stx17-syntaxin-17
#6
Kohei Arasaki, Mitsuo Tagaya
Pathogens subvert host defense systems including autophagy and apoptosis for their survival and proliferation. Legionella pneumophila is a Gram-negative bacterium that grows in alveolar macrophages and causes severe pneumonia. Early during infection Legionella secretes effector proteins that convert the plasma membrane-derived vacuole containing Legionella into an endoplasmic reticulum (ER)-like replicative vacuole. These vacuoles ultimately fuse with the ER, where the pathogen replicates. Recently, we showed that one of the effectors, Lpg1137, is a serine protease that targets the mitochondria-associated ER membrane (MAM) and degrades STX17 (syntaxin 17), a SNARE implicated in macroautophagy/autophagy as well as mitochondria dynamics and membrane trafficking in fed cells...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933603/autophagy-enables-retromer-dependent-plasma-membrane-translocation-of-slc2a1-glut-to-enhance-glucose-uptake
#7
Srirupa Roy, Jayanta Debnath
Macroautophagy/autophagy is traditionally viewed as an intracellular catabolic pathway that recycles core metabolites during starvation or stress. Recently, we found that autophagy also functions in the control of glucose uptake from the extracellular environment by facilitating cell surface expression of the glucose transporter SLC2A1/GLUT1. In response to increased glycolytic demand or acute glucose starvation, autophagosome induction titrates the RabGAP protein TBC1D5 away from its inhibitory interaction with the retromer complex and into MAP1LC3(+) compartments...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28931594/adhesion-force-and-attachment-lifetime-of-the-kif16b-px-domain-interaction-with-lipid-membranes
#8
Serapion Pyrpassopoulos, Henry Shuman, E Michael Ostap
KIF16B is a highly processive kinesin-3 family member that participates in the trafficking and tubulation of early endosomes along microtubules. KIF16B attaches to lipid cargos via a PX motif at its C-terminus, which has nanomolar affinity for bilayers containing phosphatidylinositol-3-phosphate (PI(3)P). As the PX domain has been proposed to be a primary mechanical anchor for the KIF16B-cargo attachment, we measured the adhesion forces and detachment kinetics of the PX domain as it interacts with membranes containing 2% PI(3)P and 98% phosphatidylcholine...
September 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28931526/cellubrevin-vesicle-associated-membrane-protein-3-vamp-3-mediated-endocytosis-and-trafficking-regulate-platelet-functions
#9
Meenakshi Banerjee, Smita Joshi, Jinchao Zhang, Carole L Moncman, Shilpi Yadav, Beth A Bouchard, Brian Storrie, Sidney W Whiteheart
Endocytosis is key to fibrinogen (Fg) uptake, trafficking of integrins (αIIbβ3, αvβ3) and purinergic receptors (P2Y1, P2Y12), and thus for normal platelet function. However, the molecular machinery required and possible trafficking routes are still ill-defined. To further identify elements of the platelet endocytic machinery, we examined the role of a vesicle-residing, Soluble N-ethylmaleimide Factor Attachment Protein Receptor (v-SNARE) called Cellubrevin/Vesicle-Associated Membrane Protein-3 (VAMP-3) in platelet function...
September 20, 2017: Blood
https://www.readbyqxmd.com/read/28927260/the-roles-of-the-snare-protein-sed5-in-autophagy-in-saccharomyces-cerevisiae
#10
Shenshen Zou, Dan Sun, Yongheng Liang
Autophagy is a degradation pathway in eukaryotic cells in which aging proteins and organelles are sequestered into double-membrane vesicles, termed autophagosomes, which fuse with vacuoles to hydrolyze cargo. The key step in autophagy is the formation of autophagosomes, which requires different kinds of vesicles, including COPII vesicles and Atg9- containing vesicles, to transport lipid double-membranes to the phagophore assembly site (PAS). In yeast, the cis-Golgi localized t-SNARE protein Sed5 plays a role in endoplasmic reticulum (ER)-Golgi and intra-Golgi vesicular transport...
September 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28924207/novel-ecto-tagged-integrins-reveal-their-trafficking-in-live-cells
#11
Clotilde Huet-Calderwood, Felix Rivera-Molina, Daniel V Iwamoto, Emil B Kromann, Derek Toomre, David A Calderwood
Integrins are abundant heterodimeric cell-surface adhesion receptors essential in multicellular organisms. Integrin function is dynamically modulated by endo-exocytic trafficking, however, major mysteries remain about where, when, and how this occurs in living cells. To address this, here we report the generation of functional recombinant β1 integrins with traceable tags inserted in an extracellular loop. We demonstrate that these 'ecto-tagged' integrins are cell-surface expressed, localize to adhesions, exhibit normal integrin activation, and restore adhesion in β1 integrin knockout fibroblasts...
September 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28923919/multiple-interactions-between-an-arf-gef-complex-and-charged-lipids-determine-activation-kinetics-on-the-membrane
#12
Deepti Karandur, Agata Nawrotek, John Kuriyan, Jacqueline Cherfils
Lipidated small GTPases and their regulators need to bind to membranes to propagate actions in the cell, but an integrated understanding of how the lipid bilayer exerts its effect has remained elusive. Here we focused on ADP ribosylation factor (Arf) GTPases, which orchestrate a variety of regulatory functions in lipid and membrane trafficking, and their activation by the guanine-nucleotide exchange factor (GEF) Brag2, which controls integrin endocytosis and cell adhesion and is impaired in cancer and developmental diseases...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923514/cell-polarity-and-planar-cell-polarity-pcp-in-spermatogenesis
#13
REVIEW
Haiqi Chen, Dolores D Mruk, Wing-Yee Lui, Chris K C Wong, Will M Lee, C Yan Cheng
In adult mammalian testes, spermatids, most notably step 17-19 spermatids in stage IV-VIII tubules, are aligned with their heads pointing toward the basement membrane and their tails toward the tubule lumen. On the other hand, these polarized spermatids also align across the plane of seminiferous epithelium, mimicking planar cell polarity (PCP) found in other hair cells in cochlea (inner ear). This orderly alignment of developing spermatids during spermiogenesis is important to support spermatogenesis, such that the maximal number of developing spermatids can be packed and supported by a fixed population of differentiated Sertoli cells in the limited space of the seminiferous epithelium in adult testes...
September 15, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28923401/pharmacological-blockade-of-cholesterol-trafficking-by-cepharanthine-in-endothelial-cells-suppresses-angiogenesis-and-tumor-growth
#14
Junfang Lyu, Eun Ju Yang, Sarah A Head, Nana Ai, Baoyuan Zhang, Changjie Wu, Ruo-Jing Li, Yifan Liu, Chen Yang, Yongjun Dang, Ho Jeong Kwon, Wei Ge, Jun O Liu, Joong Sup Shim
Cholesterol is an important modulator of membrane protein function and signaling in endothelial cells, thus making it an emerging target for anti-angiogenic agents. In this study, we employed a phenotypic screen that detects intracellular cholesterol distribution in endothelial cells (HUVEC) and identified 13 existing drugs as cholesterol trafficking inhibitors. Cepharanthine, an approved drug for anti-inflammatory and cancer management use, was amongst the candidates, which was selected for in-depth mechanistic studies to link cholesterol trafficking and angiogenesis...
September 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28923298/development-of-a-method-for-the-preparation-of-zirconium-89-radiolabelled-chitosan-nanoparticles-as-an-application-for-leukocyte-trafficking-with-positron-emission-tomography
#15
M Fairclough, B Ellis, H Boutin, A K P Jones, A McMahon, S Alzabin, A Gennari, C Prenant
Positron Emission Tomography is an attractive imaging modality for monitoring the migration of cells to pathological tissue. We evaluated a new method for radiolabelling leukocytes with zirconium-89 ((89)Zr) using chitosan nanoparticles (CN, Z-average size 343 ± 210nm and zeta potential +46 ± 4mV) as the carrier. We propose that cell uptake of (89)Zr-loaded CN occurred in a two-step process; cell membrane interaction with (89)Zr-loaded CN was followed by a slower cell internalisation step.
September 6, 2017: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/28922356/mathematical-modeling-and-quantitative-analysis-of-hiv-1-gag-trafficking-and-polymerization
#16
Yuewu Liu, Xiufen Zou
Gag, as the major structural protein of HIV-1, is necessary for the assembly of the HIV-1 sphere shell. An in-depth understanding of its trafficking and polymerization is important for gaining further insights into the mechanisms of HIV-1 replication and the design of antiviral drugs. We developed a mathematical model to simulate two biophysical processes, specifically Gag monomer and dimer transport in the cytoplasm and the polymerization of monomers to form a hexamer underneath the plasma membrane. Using experimental data, an optimization approach was utilized to identify the model parameters, and the identifiability and sensitivity of these parameters were then analyzed...
September 18, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28922188/new-insights-into-the-role-of-glycosylation-in-lipoprotein-metabolism
#17
Marjolein A W van den Boogert, Daniel J Rader, Adriaan G Holleboom
PURPOSE OF REVIEW: Human genetics has provided new insights into the role of protein glycosylation in regulating lipoprotein metabolism. Here we review these new developments and discuss the biological insights they provide. RECENT FINDINGS: Case descriptions of patients with congenital defects in N-glycosylation (CDG-I) frequently describe a distinct hypocholesterolemia in these rare multisystem clinical syndromes. Two novel CDGs with disturbed Golgi homeostasis and trafficking defects result in mixed glycosylation disorders, hepatic steatosis and hypercholesterolemia...
September 15, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28922150/synthesis-radiosynthesis-and-preliminary-in-vitro-and-in-vivo-evaluation-of-the-fluorinated-ceramide-trafficking-inhibitor-hpa-12-for-brain-applications
#18
Simone M Crivelli, Andreas Paulus, Jozef Markus, Matthias Bauwens, Dusan Berkes, Helga E De Vries, Monique T Mulder, Jochen Walter, Felix M Mottaghy, Mario Losen, Pilar Martinez-Martinez
Ceramide levels are increased in blood and brain tissue of Alzheimer's disease (AD) patients. Since the ceramide transporter protein (CERT) is the only known protein able to mediate non-vesicular transfer of ceramide between organelle membranes, the modulation of CERT function may impact on ceramide accumulation. The competitive CERT inhibitor N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide (HPA-12) interferes with ceramide trafficking. To understand the role of ceramide/CERT in AD, HPA-12 can be a useful tool to modulate ceramide trafficking...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28920103/existence-of-brain-5-ht1a-5-ht2a-isoreceptor-complexes-with-antagonistic-allosteric-receptor-receptor-interactions-regulating-5-ht1a-receptor-recognition
#19
Dasiel O Borroto-Escuela, Xiang Li, Alexander O Tarakanov, David Savelli, Manuel Narváez, Kirill Shumilov, Yuniesky Andrade-Talavera, Antonio Jimenez-Beristain, Bartosz Pomierny, Zaida Díaz-Cabiale, Riccardo Cuppini, Patrizia Ambrogini, Maria Lindskog, Kjell Fuxe
Studies on serotonin-selective reuptake inhibitors have established that disturbances in the ascending 5-HT neuron systems and their 5-HT receptor subtypes and collateral networks to the forebrain contribute to the etiology of major depression and are targets for treatment. The therapeutic action of serotonin-selective reuptake inhibitors is of proven effectiveness, but the mechanisms underlying their effect are still unclear. There are many 5-HT subtypes involved; some need to be blocked (e.g., 5-HT2A, 5-HT3, and 5-HT7), whereas others need to be activated (e...
August 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/28919037/a-link-between-linearmycin-biosynthesis-and-extracellular-vesicle-genesis-connects-specialized-metabolism-and-bacterial-membrane-physiology
#20
B Christopher Hoefler, Reed M Stubbendieck, N Kalyani Josyula, Sabrina M Moisan, Emma M Schulze, Paul D Straight
Specialized metabolites support bacterial competitive fitness as antibiotics, signals, pigments, and metal scavengers. Little is known about how specialized metabolites are processed and trafficked for their diverse competitive functions. Linearmycins A and B are linear polyketides with antifungal and antibacterial activity but are colony-localized in imaging mass spectrometry of Streptomyces sp. Mg1 (S. sp. Mg1). To decipher a connection between colony localization and antibiotic activity, we identified the linearmycin gene cluster and investigated linearmycin production and distribution by S...
August 24, 2017: Cell Chemical Biology
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