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https://www.readbyqxmd.com/read/27895154/kidney-tubular-ablation-of-ocrl-inpp5b-phenocopies-lowe-syndrome-tubulopathy
#1
Kazunori Inoue, Daniel M Balkin, Lijuan Liu, Ramiro Nandez, Yumei Wu, Xuefei Tian, Tong Wang, Robert Nussbaum, Pietro De Camilli, Shuta Ishibe
Lowe syndrome and Dent disease are two conditions that result from mutations of the inositol 5-phosphatase oculocerebrorenal syndrome of Lowe (OCRL) and share the feature of impaired kidney proximal tubule function. Genetic ablation of Ocrl in mice failed to recapitulate the human phenotypes, possibly because of the redundant functions of OCRL and its paralog type 2 inositol polyphosphate-5-phosphatase (INPP5B). Germline knockout of both paralogs in mice results in early embryonic lethality. We report that kidney tubule-specific inactivation of Inpp5b on a global Ocrl-knockout mouse background resulted in low molecular weight proteinuria, phosphaturia, and acidemia...
November 28, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27670760/membrane-fission-by-dynamin-what-we-know-and-what-we-need-to-know
#2
Bruno Antonny, Christopher Burd, Pietro De Camilli, Elizabeth Chen, Oliver Daumke, Katja Faelber, Marijn Ford, Vadim A Frolov, Adam Frost, Jenny E Hinshaw, Tom Kirchhausen, Michael M Kozlov, Martin Lenz, Harry H Low, Harvey McMahon, Christien Merrifield, Thomas D Pollard, Phillip J Robinson, Aurélien Roux, Sandra Schmid
The large GTPase dynamin is the first protein shown to catalyze membrane fission. Dynamin and its related proteins are essential to many cell functions, from endocytosis to organelle division and fusion, and it plays a critical role in many physiological functions such as synaptic transmission and muscle contraction. Research of the past three decades has focused on understanding how dynamin works. In this review, we present the basis for an emerging consensus on how dynamin functions. Three properties of dynamin are strongly supported by experimental data: first, dynamin oligomerizes into a helical polymer; second, dynamin oligomer constricts in the presence of GTP; and third, dynamin catalyzes membrane fission upon GTP hydrolysis...
September 26, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27566589/ermp1-a-novel-potential-oncogene-involved-in-upr-and-oxidative-stress-defense-is-highly-expressed-in-human-cancer
#3
Alberto Grandi, Alice Santi, Susanna Campagnoli, Matteo Parri, Elisa De Camilli, Chaojun Song, Boquan Jin, Aurelien Lacombe, Serenella Castori-Eppenberger, Paolo Sarmientos, Guido Grandi, Giuseppe Viale, Luigi Terracciano, Paola Chiarugi, Piero Pileri, Renata Grifantini
Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are highly activated in cancer and involved in tumorigenesis and resistance to anti-cancer therapy. UPR is becoming a promising target of anti-cancer therapies. Thus, the identification of UPR components that are highly expressed in cancer could offer new therapeutic opportunity.In this study, we demonstrate that Endoplasmic Reticulum Metallo Protease 1 (ERMP1) is broadly expressed in a high percentage of breast, colo-rectal, lung, and ovary cancers, regardless of their stage and grade...
August 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27435091/loss-of-synj1-dual-phosphatase-activity-leads-to-early-onset-refractory-seizures-and-progressive-neurological-decline
#4
Katia Hardies, Yiying Cai, Claude Jardel, Anna C Jansen, Mian Cao, Patrick May, Tania Djémié, Caroline Hachon Le Camus, Kathelijn Keymolen, Tine Deconinck, Vikas Bhambhani, Catherine Long, Samin A Sajan, Katherine L Helbig, Arvid Suls, Rudi Balling, Ingo Helbig, Peter De Jonghe, Christel Depienne, Pietro De Camilli, Sarah Weckhuysen
SYNJ1 encodes a polyphosphoinositide phosphatase, synaptojanin 1, which contains two consecutive phosphatase domains and plays a prominent role in synaptic vesicle dynamics. Autosomal recessive inherited variants in SYNJ1 have previously been associated with two different neurological diseases: a recurrent homozygous missense variant (p.Arg258Gln) that abolishes Sac1 phosphatase activity was identified in three independent families with early onset parkinsonism, whereas a homozygous nonsense variant (p.Arg136*) causing a severe decrease of mRNA transcript was found in a single patient with intractable epilepsy and tau pathology...
September 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27419871/endosome-er-contacts-control-actin-nucleation-and-retromer-function-through-vap-dependent-regulation-of-pi4p
#5
Rui Dong, Yasunori Saheki, Sharan Swarup, Louise Lucast, J Wade Harper, Pietro De Camilli
VAP (VAPA and VAPB) is an evolutionarily conserved endoplasmic reticulum (ER)-anchored protein that helps generate tethers between the ER and other membranes through which lipids are exchanged across adjacent bilayers. Here, we report that by regulating PI4P levels on endosomes, VAP affects WASH-dependent actin nucleation on these organelles and the function of the retromer, a protein coat responsible for endosome-to-Golgi traffic. VAP is recruited to retromer budding sites on endosomes via an interaction with the retromer SNX2 subunit...
July 14, 2016: Cell
https://www.readbyqxmd.com/read/27328312/fat1-a-potential-target-for-monoclonal-antibody-therapy-in-colon-cancer
#6
Piero Pileri, Susanna Campagnoli, Alberto Grandi, Matteo Parri, Elisa De Camilli, Chaojun Song, Luisa Ganfini, Aurelien Lacombe, Ilaria Naldi, Paolo Sarmientos, Caterina Cinti, Boquan Jin, Guido Grandi, Giuseppe Viale, Luigi Terracciano, Renata Grifantini
BACKGROUND: Colorectal cancer (CRC) is one of the major causes of cancer-associated mortality worldwide. The currently approved therapeutic agents have limited efficacy. METHODS: The atypical cadherin FAT1 was discovered as a novel CRC-associated protein by using a monoclonal antibody (mAb198.3). FAT1 expression was assessed in CRC cells by immunohistochemistry (IHC), immunoblots, flow cytometry and confocal microscopy. In addition, in vitro and in vivo tumour models were done to assess FAT1 potential value for therapeutic applications...
June 28, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27252358/the-endocytic-activity-of-the-flagellar-pocket-in-trypanosoma-brucei-is-regulated-by-an-adjacent-phosphatidylinositol-phosphate-kinase
#7
Lars Demmel, Katy Schmidt, Louise Lucast, Katharina Havlicek, Armin Zankel, Tina Koestler, Viktoria Reithofer, Pietro de Camilli, Graham Warren
No abstract text is available yet for this article.
June 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27067338/icespy009-a-conjugative-genetic-element-carrying-mef-e-in-streptococcus-pyogenes
#8
Maria Del Grosso, Romina Camilli, Ermanno Rizzi, Alessandro Pietrelli, Gianluca De Bellis, Annalisa Pantosti
Efflux-mediated macrolide resistance due to mef(E) and mel, carried by the mega element, is common in Streptococcus pneumoniae, for which it was originally characterized, but it is rare in Streptococcus pyogenes In S. pyogenes, mega was previously found to be enclosed in Tn2009, a composite genetic element of the Tn916 family containing tet(M) and conferring erythromycin and tetracycline resistance. In this study, S. pyogenes isolates containing mef(E), apparently not associated with other resistance determinants, were examined to characterize the genetic context of mega...
July 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27065097/control-of-plasma-membrane-lipid-homeostasis-by-the-extended-synaptotagmins
#9
Yasunori Saheki, Xin Bian, Curtis M Schauder, Yujin Sawaki, Michal A Surma, Christian Klose, Frederic Pincet, Karin M Reinisch, Pietro De Camilli
Acute metabolic changes in plasma membrane (PM) lipids, such as those mediating signalling reactions, are rapidly compensated by homeostatic responses whose molecular basis is poorly understood. Here we show that the extended synaptotagmins (E-Syts), endoplasmic reticulum (ER) proteins that function as PtdIns(4,5)P2- and Ca(2+)-regulated tethers to the PM, participate in these responses. E-Syts transfer glycerolipids between bilayers in vitro, and this transfer requires Ca(2+) and their lipid-harbouring SMP domain...
May 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/26913545/aminomethylnaphthoquinones-and-hsv-1-in-vitro-and-in-silico-evaluations-of-potential-antivirals
#10
Camilly P Pires de Mello, Nathália S Sardoux, Luciana Terra, Leonardo C Amorim, Maria D Vargas, Gustavo B da Silva, Helena C Castro, Viveca A Giongo, Lucianne F Madeira, Izabel Cnp Paixão
BACKGROUND: Herpes simplex viruses (HSV) are leading causes of human infections which result in severe manifestations, especially in neonates, immunocompromised and/or transplanted individuals. Current HSV type-1 (HSV-1) resistance to standard antiviral agents is a therapeutic challenge, especially for treating immunocompromised patients. METHODS: Herein we describe the promising antiviral profile of three 2-aminomethyl-3-hydroxy-1,4-naphthoquinones against HSV-1 using Vero cells...
2016: Antiviral Therapy
https://www.readbyqxmd.com/read/26726828/herpes-simplex-virus-type-1-replication-latency-reactivation-and-its-antiviral-targets
#11
Camilly P Pires de Mello, David C Bloom, Izabel Cnp Paixão
Infection by herpes simplex virus type-1 (HSV-1) causes several diseases, ranging from cutaneous, oral and genital infections to fatal encephalitis. Despite the availability of antiviral therapies on the market, their efficacies are incomplete, and new cases of resistant strains arise, mainly in the immunocompromised, but also recently documented in immunocompetent patients. Over the last decades a lot has been discovered about the molecular basis of infection which has been of great benefit to the investigation of new anti-HSV-1 molecules...
2016: Antiviral Therapy
https://www.readbyqxmd.com/read/26686281/smp-domain-proteins-at-membrane-contact-sites-structure-and-function
#12
REVIEW
Karin M Reinisch, Pietro De Camilli
SMP-domains are found in proteins that localize to membrane contact sites. Elucidation of the properties of these proteins gives clues as to the molecular bases underlying processes that occur at such sites. Described here are recent discoveries concerning the structure, function, and regulation of the Extended-Synaptotagmin proteins and ERMES complex subunits, SMP-domain proteins at endoplasmic reticulum (ER)-plasma membrane and ER-mitochondrial contacts, respectively. They act as tethers contributing to the architecture of these sites and as lipid transporters that convey glycerolipids between apposed membranes...
August 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26571211/the-leukodystrophy-protein-fam126a-hyccin-regulates-ptdins-4-p-synthesis-at-the-plasma%C3%A2-membrane
#13
Jeremy M Baskin, Xudong Wu, Romain Christiano, Michael S Oh, Curtis M Schauder, Elisabetta Gazzerro, Mirko Messa, Simona Baldassari, Stefania Assereto, Roberta Biancheri, Federico Zara, Carlo Minetti, Andrea Raimondi, Mikael Simons, Tobias C Walther, Karin M Reinisch, Pietro De Camilli
Genetic defects in myelin formation and maintenance cause leukodystrophies, a group of white matter diseases whose mechanistic underpinnings are poorly understood. Hypomyelination and congenital cataract (HCC), one of these disorders, is caused by mutations in FAM126A, a gene of unknown function. We show that FAM126A, also known as hyccin, regulates the synthesis of phosphatidylinositol 4-phosphate (PtdIns(4)P), a determinant of plasma membrane identity. HCC patient fibroblasts exhibit reduced PtdIns(4)P levels...
January 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/26552687/analysis-of-the-phosphoinositide-composition-of-subcellular-membrane-fractions
#14
Deborah A Sarkes, Lucia E Rameh
Phosphoinositides play critical roles in the transduction of extracellular signals through the plasma membrane and also in endomembrane events important for vesicle trafficking and organelle function (Di Paolo and De Camilli, Nature 443(7112):651-657, 2006). The response triggered by these lipids is heavily dependent on the microenvironment in which they are found. HPLC analysis of labeled phosphoinositides allows quantification of the levels of each phosphoinositide species relative to their precursor, phosphatidylinositol...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/26439542/op-1-artificial-oesophagus-engineering-in-a-3d-dynamic-culture
#15
C Camilli, L Urbani, F Scottoni, C Crowley, R R Wong, P Maghsoudlou, M E Alvarez Fallas, M Lowdell, M Birchall, G Cossu, P De Coppi
No abstract text is available yet for this article.
October 2015: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/26373379/negatively-charged-aunp-modified-with-monoclonal-antibody-against-novel-tumor-antigen-fat1-for-tumor-targeting
#16
Li Fan, Susanna Campagnoli, Hong Wu, Alberto Grandi, Matteo Parri, Elisa De Camilli, Guido Grandi, Giuseppe Viale, Piero Pileri, Renata Grifantini, Chaojun Song, Boquan Jin
BACKGROUND: Herein, we demonstrated the use of a newly generated anti FAT1 antibody (clone mAB198.3) for intracellular delivery of anionic gold NPs, to form active targeting Au nanoparticles with high payload characteristics. METHODS: In vitro characterizations were determined by DLS, confocal microscopy, TEM, western blot, MALDI-TOF MS/MS analysis, MTT, ICP-MS and flow cytometry analysis. In vivo targeting efficacy was investigated by in vivo bio-imaging study and ICP-MS...
2015: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/26299204/ultrafast-non-radiative-decay-of-gas-phase-nucleosides
#17
Simone De Camillis, Jordan Miles, Grace Alexander, Omair Ghafur, Ian D Williams, Dave Townsend, Jason B Greenwood
The ultrafast photo-physical properties of DNA are crucial in providing a stable basis for life. Although the DNA bases efficiently absorb ultraviolet (UV) radiation, this energy can be dissipated to the surrounding environment by the rapid conversion of electronic energy to vibrational energy within about a picosecond. The intrinsic nature of this internal conversion process has previously been demonstrated through gas phase experiments on the bases, supported by theoretical calculations. De-excitation rates appear to be accelerated when individual bases are hydrogen bonded to solvent molecules or their complementary Watson-Crick pair...
September 28, 2015: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/26278614/resonantly-enhanced-multiphoton-ionization-spectrum-of-the-neutral-green-fluorescent-protein-chromophore
#18
Jason B Greenwood, Jordan Miles, Simone De Camillis, Peter Mulholland, Lijuan Zhang, Michael A Parkes, Helen C Hailes, Helen H Fielding
The photophysics of the green fluorescent protein is governed by the electronic structure of the chromophore at the heart of its β-barrel protein structure. We present the first two-color, resonance-enhanced, multiphoton ionization spectrum of the isolated neutral chromophore in vacuo with supporting electronic structure calculations. We find the absorption maximum to be 3.65 ± 0.05 eV (340 ± 5 nm), which is blue-shifted by 0.5 eV (55 nm) from the absorption maximum of the protein in its neutral form. Our results show that interactions between the chromophore and the protein have a significant influence on the electronic structure of the neutral chromophore during photoabsorption and provide a benchmark for the rational design of novel chromophores as fluorescent markers or photomanipulators...
October 16, 2014: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/26251044/increased-levels-of-interleukin-6-exacerbate-the-dystrophic-phenotype-in-mdx-mice
#19
Laura Pelosi, Maria Grazia Berardinelli, Laura Forcina, Elisa Spelta, Emanuele Rizzuto, Carmine Nicoletti, Carlotta Camilli, Erika Testa, Angela Catizone, Fabrizio De Benedetti, Antonio Musarò
Duchenne muscular dystrophy (DMD) is characterized by progressive lethal muscle degeneration and chronic inflammatory response. The mdx mouse strain has served as the animal model for human DMD. However, while DMD patients undergo extensive necrosis, the affected muscles of adult mdx mice rapidly regenerates and regains structural and functional integrity. The basis for the mild effects observed in mice compared with the lethal consequences in humans remains unknown. In this study, we provide evidence that interleukin-6 (IL-6) is causally linked to the pathogenesis of muscular dystrophy...
November 1, 2015: Human Molecular Genetics
https://www.readbyqxmd.com/read/26206935/intracellular-transport-pi4p-phosphatidylserine-countertransport-at-orp5-and-orp8-mediated-er-plasma-membrane-contacts
#20
Jeeyun Chung, Federico Torta, Kaori Masai, Louise Lucast, Heather Czapla, Lukas B Tanner, Pradeep Narayanaswamy, Markus R Wenk, Fubito Nakatsu, Pietro De Camilli
Lipid transfer between cell membrane bilayers at contacts between the endoplasmic reticulum (ER) and other membranes help to maintain membrane lipid homeostasis. We found that two similar ER integral membrane proteins, oxysterol-binding protein (OSBP)-related protein 5 (ORP5) and ORP8, tethered the ER to the plasma membrane (PM) via the interaction of their pleckstrin homology domains with phosphatidylinositol 4-phosphate (PI4P) in this membrane. Their OSBP-related domains (ORDs) harbored either PI4P or phosphatidylserine (PS) and exchanged these lipids between bilayers...
July 24, 2015: Science
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