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https://www.readbyqxmd.com/read/28550115/involvement-of-cell-surface-90-kda-heat-shock-protein-hsp90-in-pattern-recognition-by-human-monocyte-derived-macrophages
#1
Małgorzata Bzowska, Anna Nogieć, Krystian Bania, Magdalena Zygmunt, Mirosław Zarębski, Jerzy Dobrucki, Krzysztof Guzik
Heat shock proteins (HSPs) are typical intracellular chaperones which also appear on the cell surface and in extracellular milieu. HSP90, which chaperones many proteins involved in signal transduction, is also a regular component of LPS-signaling complexes on Mϕ. As LPS is a prototypical PAMP, we speculated that HSP90 is engaged in pattern recognition by professional phagocytes. In this report, we provide the first evidence, to our knowledge, of the geldanamycin (Ge)-inhibitable HSP90 on the surface of live monocyte-derived Mϕs (hMDMs)...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550045/pacsin2-accelerates-nephrin-trafficking-and-is-up-regulated-in-diabetic-kidney-disease
#2
Vincent Dumont, Tuomas A Tolvanen, Sara Kuusela, Hong Wang, Tuula A Nyman, Sonja Lindfors, Jukka Tienari, Harry Nisen, Shiro Suetsugu, Markus Plomann, Hiroshi Kawachi, Sanna Lehtonen
Nephrin is a core component of podocyte (glomerular epithelial cell) slit diaphragm and is required for kidney ultrafiltration. Down-regulation or mislocalization of nephrin has been observed in diabetic kidney disease (DKD), characterized by albuminuria. Here, we investigate the role of protein kinase C and casein kinase 2 substrate in neurons 2 (PACSIN2), a regulator of endocytosis and recycling, in the trafficking of nephrin and development of DKD. We observe that PACSIN2 is up-regulated and nephrin mislocalized in podocytes of obese Zucker Diabetic Fatty (ZDF) rats that have altered renal function...
May 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28542518/rnf41-interacts-with-the-vps52-subunit-of-the-garp-and-earp-complexes
#3
Delphine Masschaele, Leentje De Ceuninck, Joris Wauman, Dieter Defever, Frank Stenner, Sam Lievens, Frank Peelman, Jan Tavernier
RNF41 (Ring Finger Protein 41) is an E3 ubiquitin ligase involved in the intracellular sorting and function of a diverse set of substrates. Next to BRUCE and Parkin, RNF41 can directly ubiquitinate ErbB3, IL-3, EPO and RARα receptors or downstream signaling molecules such as Myd88, TBK1 and USP8. In this way it can regulate receptor signaling and routing. To further elucidate the molecular mechanism behind the role of RNF41 in intracellular transport we performed an Array MAPPIT (Mammalian Protein-Protein Interaction Trap) screen using an extensive set of proteins derived from the human ORFeome collection...
2017: PloS One
https://www.readbyqxmd.com/read/28536357/glycosylated-triterpenoids-as-endosomal-escape-enhancers-in-targeted-tumor-therapies
#4
REVIEW
Hendrik Fuchs, Nicole Niesler, Alexandra Trautner, Simko Sama, Gerold Jerz, Hossein Panjideh, Alexander Weng
Protein-based targeted toxins play an increasingly important role in targeted tumor therapies. In spite of their high intrinsic toxicity, their efficacy in animal models is low. A major reason for this is the limited entry of the toxin into the cytosol of the target cell, which is required to mediate the fatal effect. Target receptor bound and internalized toxins are mostly either recycled back to the cell surface or lysosomally degraded. This might explain why no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date although more than 500 targeted toxins have been developed within the last decades...
March 29, 2017: Biomedicines
https://www.readbyqxmd.com/read/28533221/cd9-regulates-mhc-ii-trafficking-in-monocyte-derived-dendritic-cells
#5
Vera Rocha-Perugini, Gloria Martínez Del Hoyo, José Maria González-Granado, Marta Ramírez-Huesca, Virginia Zorita, Eric Rubinstein, Claude Boucheix, Francisco Sánchez-Madrid
Antigen presentation by dendritic cells (DCs) stimulates naïve CD4(+) T cells, triggering T cell activation and the adaptive arm of the immune response. Newly synthesized major histocompatibility complex class II molecules (MHC-II) accumulate at MHC-II-enriched endosomal compartments, and are transported to the plasma membrane of DCs after binding to antigenic peptides to enable antigen presentation. In DCs, MHC-II molecules are included in tetraspanin-enriched microdomains (TEMs). However, the role of tetraspanin CD9 in these processes remains largely undefined...
May 22, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28521960/yeast-dynamin-associates-with-the-garp-tethering-complex-for-endosome-to-golgi-traffic
#6
Uma Saimani, Jared Smothers, Hyoeun McDermott, Pelin Makaraci, Kyoungtae Kim
Yeast dynamin, Vacuolar Protein Sorting 1 (Vps1), has been implicated in recycling traffic from the endosome to the trans-Golgi network (TGN). Previous research showed a genetic interaction of Vps1 with all components of the GARP tethering complex, which anchors vesicles at the late Golgi membrane. We used the yeast two-hybrid system and have identified a 33 amino acid segment of Vps51, a GARP subunit, that interacts with Vps1. Based on sequence homology between Vps51 and its mammalian homolog Ang2 in the 33 amino acids stretch, we identified two key residues of Vps51, E127 and Y129, that bind Vps1...
May 8, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28521780/ultrasound-and-microbubble-induced-release-from-intracellular-compartments
#7
Farah Hussein, Costin Antonescu, Raffi Karshafian
BACKGROUND: Ultrasound and microbubbles (USMB) have been shown to enhance the intracellular uptake of molecules, generally thought to occur as a result of sonoporation. The underlying mechanism associated with USMB-enhanced intracellular uptake such as membrane disruption and endocytosis may also be associated with USMB-induced release of cellular materials to the extracellular milieu. This study investigates USMB effects on the molecular release from cells through membrane-disruption and exocytosis...
May 18, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28487419/membrane-depolarization-activates-bk-channels-through-rock-mediated-%C3%AE-1-subunit-surface-trafficking-to-limit-vasoconstriction
#8
M Dennis Leo, Xue Zhai, Padmapriya Muralidharan, Korah P Kuruvilla, Simon Bulley, Frederick A Boop, Jonathan H Jaggar
Membrane depolarization of smooth muscle cells (myocytes) in the small arteries that regulate regional organ blood flow leads to vasoconstriction. Membrane depolarization also activates large-conductance calcium (Ca(2+))-activated potassium (BK) channels, which limits Ca(2+) channel activity that promotes vasoconstriction, thus leading to vasodilation. We showed that in human and rat arterial myocytes, membrane depolarization rapidly increased the cell surface abundance of auxiliary BK β1 subunits but not that of the pore-forming BKα channels...
May 9, 2017: Science Signaling
https://www.readbyqxmd.com/read/28482024/vps35-in-cooperation-with-lrrk2-regulates-synaptic-vesicle-endocytosis-through-the-endosomal-pathway-in-drosophila
#9
Tsuyoshi Inoshita, Taku Arano, Yuka Hosaka, Hongrui Meng, Yujiro Umezaki, Sakiko Kosugi, Takako Morimoto, Masato Koike, Hui-Yun Chang, Yuzuru Imai, Nobutaka Hattori
Mutations of the retromer component Vps35 and endosomal kinase LRRK2 are linked to autosomal dominant forms of familial Parkinson's disease (PD). However, the physiological and pathological roles of Vps35 and LRRK2 in neuronal functions are poorly understood. Here, we demonstrated that the loss of Drosophila Vps35 (dVps35) affects synaptic vesicle recycling, dopaminergic synaptic release and sleep behavior associated with dopaminergic activity, which is rescued by the expression of wild-type dVps35 but not the PD-associated mutant dVps35 D647N...
May 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28478994/emerging-paradigms-of-g-protein-coupled-receptor-dephosphorylation
#10
REVIEW
Andrea Kliewer, Rainer K Reinscheid, Stefan Schulz
Elucidation of the molecular mechanisms underlying G protein-coupled receptor (GPCR) dephosphorylation remains a major challenge. While specific GPCR phosphatases (GRPs) have eluded identification, prevailing models propose that receptors must first internalize into acidic endosomes to become dephosphorylated in a housekeeping-like process. Recently, phosphosite-specific antibodies, combined with siRNAs targeting specific phosphatase transcripts, have facilitated the identification of distinct protein phosphatase 1 (PP1) and PP2 catalytic subunits as bona fide GRPs...
May 4, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28475195/quantitative-image-cytometry-for-analyzing-intracellular-trafficking-of-g-protein-coupled-receptors-on-a-chemical-trapping-single-cell-array
#11
Modong Tan, Satoshi Yamaguchi, Shinya Yamahira, Motonao Nakamura, Teruyuki Nagamune
G protein-coupled receptors (GPCRs) are important targets in medical and pharmaceutical research fields, because they play key roles in a variety of biological processes. Recently, intracellular trafficking of GPCRs involving endosomal internalization and recycling to the plasma membrane has been studied as a regulation mechanism for GPCR activities. However, the absence of a quantitative single-cell analysis method has hampered conditional GPCR trafficking studies and the possibility of gaining significant insights into the mechanism of regulation of GPCR signaling...
May 5, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28471261/rab17-mediates-intermixing-of-phagocytosed-apoptotic-cells-with-recycling-endosomes
#12
Charles Yin, Dean Argintaru, Bryan Heit
Efferocytosis-the phagocytic removal of apoptotic cells-is required for preventing the presentation of apoptotic cell-derived antigens. This process is regulated by Rab17-dependent sorting of efferocytosed cargos from the phagolysosome to recycling endosomes. In this study we demonstrate that Rab17 is rapidly recruited to efferosomes, followed by migration of the efferosome to the cell center where it intermixes with lysosomes and undergoes Rab17-dependent vesiculation. These efferosome-derived vesicles then traffic in a Rab17-dependent manner to the cell periphery, where they transfer cargo to recycling endosomes...
May 4, 2017: Small GTPases
https://www.readbyqxmd.com/read/28471021/syntaxin-4-mediates-endosome-recycling-for-lytic-granule-exocytosis-in-cytotoxic-t-lymphocytes
#13
Waldo A Spessott, Maria L Sanmillan, Vineet V Kulkarni, Margaret E McCormick, Claudio G Giraudo
Adaptive and innate immunity utilize the perforin-killing pathway to eliminate virus-infected or cancer cells. Cytotoxic T-lymphocytes (CTLs) and Natural Killer cells mediate this process by releasing toxic proteins at the contact area with target cells known as immunological synapse (IS). Formation of a stable IS and exocytosis of toxic proteins requires persistent fusion of Rab11a recycling endosomes with the plasma membrane (PM) that may assure the delivery of key effector proteins. Despite the importance of the recycling endosomal compartment, the membrane fusion proteins that control this process at the IS remain elusive...
May 4, 2017: Traffic
https://www.readbyqxmd.com/read/28468881/mutations-in-the-transmembrane-domain-and-cytoplasmic-tail-of-hendra-virus-fusion-protein-disrupt-virus-like-particle-assembly
#14
Nicolás Cifuentes-Muñoz, Weina Sun, Greeshma Ray, Phuong Tieu Schmitt, Stacy Webb, Kathleen Gibson, Rebecca Ellis Dutch, Anthony P Schmitt
Hendra virus (HeV) is a zoonotic paramyxovirus that causes deadly illness in horses and humans. An intriguing feature of HeV is the utilization of endosomal protease for activation of the viral fusion protein (F). Here, we investigated how F endosomal trafficking impacts HeV assembly. We found that HeV matrix (M) and F proteins each induced particle release when expressed alone, but their co-expression led to coordinated assembly of virus-like particles (VLPs) that were morphologically and physically distinct from M-alone or F-alone VLPs...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28457591/from-mucolipidosis-type-iv-to-ebola-trpml-and-two-pore-channels-at-the-crossroads-of-endo-lysosomal-trafficking-and-disease
#15
REVIEW
Christian Grimm, Elisabeth Butz, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
What do lysosomal storage disorders such as mucolipidosis type IV have in common with Ebola, cancer cell migration, or LDL-cholesterol trafficking? LDL-cholesterol, certain bacterial toxins and viruses, growth factors, receptors, integrins, macromolecules destined for degradation or secretion are all sorted and transported via the endolysosomal system (ES). There are several pathways known in the ES, e.g. the degradation, the recycling, or the retrograde trafficking pathway. The ES comprises early and late endosomes, lysosomes and recycling endosomes as well as autophagosomes and lysosome related organelles...
April 23, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28449947/barcoding-of-gpcr-trafficking-and-signaling-through-the-various-trafficking-roadmaps-by-compartmentalized-signaling-networks
#16
REVIEW
Suleiman W Bahouth, Mohammed M Nooh
Proper signaling by G protein coupled receptors (GPCR) is dependent on the specific repertoire of transducing, enzymatic and regulatory kinases and phosphatases that shape its signaling output. Activation and signaling of the GPCR through its cognate G protein is impacted by G protein-coupled receptor kinase (GRK)-imprinted "barcodes" that recruit β-arrestins to regulate subsequent desensitization, biased signaling and endocytosis of the GPCR. The outcome of agonist-internalized GPCR in endosomes is also regulated by sequence motifs or "barcodes" within the GPCR that mediate its recycling to the plasma membrane or retention and eventual degradation as well as its subsequent signaling in endosomes...
April 24, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28441569/the-cytoskeleton-autophagy-connection
#17
REVIEW
David J Kast, Roberto Dominguez
Actin cytoskeleton dynamics play vital roles in most forms of intracellular trafficking by promoting the biogenesis and transport of vesicular cargoes. Mounting evidence indicates that actin dynamics and membrane-cytoskeleton scaffolds also have essential roles in macroautophagy, the process by which cellular waste is isolated inside specialized vesicles called autophagosomes for recycling and degradation. Branched actin polymerization is necessary for the biogenesis of autophagosomes from the endoplasmic reticulum (ER) membrane...
April 24, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28436498/integrative-meta-modeling-identifies-endocytic-vesicles-late-endosome-and-the-nucleus-as-the-cellular-compartments-primarily-directing-rtk-signaling
#18
Jared C Weddell, Princess I Imoukhuede
Recently, intracellular receptor signaling has been identified as a key component mediating cell responses for various receptor tyrosine kinases (RTKs). However, the extent each endocytic compartment (endocytic vesicle, early endosome, recycling endosome, late endosome, lysosome and nucleus) contributes to receptor signaling has not been quantified. Furthermore, our understanding of endocytosis and receptor signaling is complicated by cell- or receptor-specific endocytosis mechanisms. Therefore, towards understanding the differential endocytic compartment signaling roles, and identifying how to achieve signal transduction control for RTKs, we delineate how endocytosis regulates RTK signaling...
May 22, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28424231/mroh1-a-lysosomal-regulator-localised-by-wash-generated-actin
#19
Peter A Thomason, Jason S King, Robert H Insall
The steps leading to constitutive exocytosis are poorly understood. In Dictyostelium WASH complex mutants, exocytosis is blocked, so cells that take up fluorescent dextran from the medium retain it and remain fluorescent. Here we establish a FACS-based method to select cells that retain fluorescent dextran, allowing identification of mutants with disrupted exocytosis. Screening a pool of random mutants identified the WASH complex, as expected, and multiple mutants in the conserved HEAT-repeat containing protein Mroh1...
April 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28415156/endocytosis-of-tight-junction-proteins-and-the-regulation-of-degradation-and-recycling
#20
REVIEW
Svetlana M Stamatovic, Allison M Johnson, Nikola Sladojevic, Richard F Keep, Anuska V Andjelkovic
Internalization of tight junction (TJ) proteins from the plasma membrane is a pivotal mechanism regulating TJ plasticity and function in both epithelial and endothelial barrier tissues. Once internalized, the TJ proteins enter complex vesicular machinery, where further trafficking is directly dependent on the initiating stimulus and downstream signaling pathways that regulate the sorting and destiny of TJ proteins, as well as on cell and barrier responses. The destiny of internalized TJ proteins is recycling to the plasma membrane or sorting to late endosomes and degradation...
April 17, 2017: Annals of the New York Academy of Sciences
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