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Recycling endosome

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https://www.readbyqxmd.com/read/28630093/dendritic-cell-sensing-of-hydrophobic-di-and-triacylated-lipopeptides-self-assembled-within-synthetic-virus-like-particles
#1
Rajni Sharma, Arin Ghasparian, John A Robinson, Kenneth C McCullough
Dendritic cells (DCs) play critical roles in developing immune defenses. One important aspect is interaction with pathogen-associated molecular patterns (PAMPs)/danger-associated molecular patterns, including di- and triacylated lipopeptides. Isolated or synthetic lipopeptides are potent vaccine adjuvants, interacting with cell surface TLR2 heterodimers. In contrast, deep embedment within bacteria cell walls would impair lipopeptide interaction with cell surface TLR2, requiring degradation for PAMP recognition...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28626083/cellular-and-disease-functions-of-the-prader-willi-syndrome-gene-magel2
#2
REVIEW
Klementina Fon Tacer, Patrick Ryan Potts
Melanoma antigen L2 (MAGEL2 or MAGE-L2) is a member of the MAGE family of ubiquitin ligase regulators. It is maternally imprinted and often paternally deleted or mutated in the related neurodevelopmental syndromes, Prader-Willi Syndrome (PWS) and Schaaf-Yang Syndrome (SHFYNG). MAGEL2 is highly expressed in the hypothalamus and plays an important role in a fundamental cellular process that recycles membrane proteins from endosomes through the retromer sorting pathway. MAGEL2 is part of a multi-subunit protein complex consisting of MAGEL2, the TRIM27 E3 ubiquitin ligase, and the USP7 deubiquitinating enzyme...
June 16, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28626000/baiap3-a-c2-domain-containing-munc13-protein-controls-the-fate-of-dense-core-vesicles-in-neuroendocrine-cells
#3
Xingmin Zhang, Shan Jiang, Kelly A Mitok, Lingjun Li, Alan D Attie, Thomas F J Martin
Dense-core vesicle (DCV) exocytosis is a SNARE (soluble N-ethylmaleimide-sensitive fusion attachment protein receptor)-dependent anterograde trafficking pathway that requires multiple proteins for regulation. Several C2 domain-containing proteins are known to regulate Ca(2+)-dependent DCV exocytosis in neuroendocrine cells. In this study, we identified others by screening all (∼139) human C2 domain-containing proteins by RNA interference in neuroendocrine cells. 40 genes were identified, including several encoding proteins with known roles (CAPS [calcium-dependent activator protein for secretion 1], Munc13-2, RIM1, and SYT10) and many with unknown roles...
June 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28622163/novel-roles-for-mucin-1-in-the-kidney
#4
Mohammad M Al-Bataineh, Rebecca P Hughey
PURPOSE OF REVIEW: Recent studies in the kidney have revealed that the well characterized tumor antigen mucin 1 (MUC1/Muc1) also has numerous functions in the normal and injured kidney. RECENT FINDINGS: Mucin 1 is a transmembrane mucin with a robust glycan-dependent apical targeting signal and efficient recycling from endosomes. It was recently reported that the TRPV5 calcium channel is stabilized on the cell surface by galectin-dependent cross-linking to mucin 1, providing a novel mechanism for regulation of ion channels and normal electrolyte balance...
June 15, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28604748/isoprenylcysteine-carboxylmethyltransferase-function-is-essential-for-rab4a-mediated-integrin-%C3%AE-3-recycling-cell-migration-and-cancer-metastasis
#5
M T Do, T F Chai, P J Casey, M Wang
Isoprenylcysteine carboxylmethyltransferase (ICMT) catalyzes the post-translational modification of RAB GTPases that contain C-terminal CXC motifs. However, the functional impact of this modification on RAB proteins has not been actively explored. We found that inhibition of ICMT significantly reduced cell migration in vitro and cancer invasion and metastasis in vivo. This role of ICMT was found to be mediated by RAB4A, an essential regulator of the fast recycling of integrin β3. Integrin β3 regulates cell polarity and migration when localized appropriately to the plasma membrane, thereby having an essential role in cancer metastasis...
June 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28602638/autophagy-dependent-shuttling-of-tbc1d5-controls-plasma-membrane-translocation-of-glut1-and-glucose-uptake
#6
Srirupa Roy, Andrew M Leidal, Jordan Ye, Sabrina M Ronen, Jayanta Debnath
Autophagy traditionally sustains metabolism in stressed cells by promoting intracellular catabolism and nutrient recycling. Here, we demonstrate that in response to stresses requiring increased glycolytic demand, the core autophagy machinery also facilitates glucose uptake and glycolytic flux by promoting cell surface expression of the glucose transporter GLUT1/Slc2a1. During metabolic stress, LC3(+) autophagic compartments bind and sequester the RabGAP protein TBC1D5 away from its inhibitory interactions with the retromer complex, thereby enabling retromer recruitment to endosome membranes and GLUT1 plasma membrane translocation...
June 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28589556/characterization-of-functional-%C3%AE-opioid-receptor-turnover-in-rat-locus-coeruleus-an-electrophysiological-and-immunocytochemical-study
#7
María Carmen Medrano, María Teresa Santamarta, Patricia Pablos, Zigor Aira, Itsaso Buesa, Jon Jatsu Azkue, Aitziber Mendiguren, Joseba Pineda
BACKGROUND AND PURPOSE: Regulation of μ receptor (MOR) dynamics such as MOR trafficking is a possible mechanism underlying opioid tolerance that contributes to inefficient recycling of opioid responses. We aimed to characterize the functional MOR turnover in the noradrenergic nucleus locus coeruleus (LC). EXPERIMENTAL APPROACH: We measured opioid effect by single-unit extracellular recordings of LC neurons from rat brain slices. Immunocytochemical techniques were also used to evaluate MOR trafficking...
June 7, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28582732/the-dynamics-and-endocytosis-of-flot1-protein-in-response-to-flg22-in-arabidopsis
#8
Meng Yu, Haijiao Liu, Ziyi Dong, Jianwei Xiao, Bodan Su, Lusheng Fan, George Komis, Jozef Šamaj, Jinxing Lin, Ruili Li
Membrane microdomains play vital roles in the process of bacterial infection. The membrane microdomain-associated protein Flot1 acts in an endocytic pathway and is required for seedling development, however, whether Flot1 is a part of host defense mechanisms remains unknown. During an analysis of callose deposition, we found that Flot1 amiRNAi mutants exhibited defects in response to flg22. Using variable-angle total internal reflection fluorescence microscopy (VA-TIRFM), structured illumination microscopy (SIM) and fluorescence cross spectroscopy (FCS), we determined that the dynamic behavior of GFP-Flot1 in Arabidopsis thaliana cotyledon epidermal cells changed significantly in plants treated with the elicitor flg22...
May 19, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28576874/bloc-1-is-required-for-selective-membrane-protein-trafficking-from-endosomes-to-primary-cilia
#9
William J Monis, Victor Faundez, Gregory J Pazour
Primary cilia perceive the extracellular environment through receptors localized in the ciliary membrane, but mechanisms directing specific proteins to this domain are poorly understood. To address this question, we knocked down proteins potentially important for ciliary membrane targeting and determined how this affects the ciliary trafficking of fibrocystin, polycystin-2, and smoothened. Our analysis showed that fibrocystin and polycystin-2 are dependent on IFT20, GMAP210, and the exocyst complex, while smoothened delivery is largely independent of these components...
June 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28576743/internalization-and-localization-of-basal-insulin-peglispro-in-cells
#10
Julie S Moyers, Catherine B Volk, Julia X C Cao, Chen Zhang, Liyun Ding, Vladislav V Kiselyov, M Dodson Michael
BACKGROUND: Basal insulin peglispro (BIL) is a novel, PEGylated insulin lispro that has a large hydrodynamic size compared with insulin lispro. It has a prolonged duration of action, which is related to a delay in insulin absorption and a reduction in clearance. Given the different physical properties of BIL compared with native insulin and insulin lispro, it is important to assess the cellular internalization characteristics of the molecule. METHODS AND MATERIALS: Using immunofluorescent confocal imaging, we compared the cellular internalization and localization patterns of BIL, biosynthetic human insulin, and insulin lispro...
May 30, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28574834/the-collagen-receptor-uparap-endo180-as-a-novel-target-for-antibody-drug-conjugate-mediated-treatment-of-mesenchymal-and-leukemic-cancers
#11
Christoffer Fagernæs Nielsen, Sander Maarten van Putten, Ida Katrine Lund, Maria Carlsén Melander, Kirstine Sandal Nørregaard, Henrik Jessen Jürgensen, Kristian Reckzeh, Kristine Rothaus Christensen, Signe Ziir Ingvarsen, Henrik Gårdsvoll, Kamilla Ellermann Jensen, Petra Hamerlik, Lars Henning Engelholm, Niels Behrendt
A key task in developing the field of personalized cancer therapy is the identification of novel molecular targets that enable treatment of cancers not susceptible to other means of specific therapy. The collagen receptor uPARAP/Endo180 is overexpressed by malignant cells in several non-epithelial cancers, notably including sarcomas, glioblastomas and subsets of acute myeloid leukemia. In contrast, in healthy adult individuals, expression is restricted to minor subsets of mesenchymal cells. Functionally, uPARAP/Endo180 is a rapidly recycling endocytic receptor that delivers its cargo directly into the endosomal-lysosomal system, thus opening a potential route of entry into receptor-positive cells...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28568905/tmem230-how-does-it-fit-in-the-etiology-and-pathogenesis-of-parkinson-s-disease
#12
REVIEW
Wim Mandemakers, Marialuisa Quadri, Maria Stamelou, Vincenzo Bonifati
Mutations in the transmembrane protein 230 (TMEM230) gene were recently identified in a large Canadian pedigree and 7 smaller Chinese families, nominating TMEM230 as the third gene causing a Mendelian form of late onset Parkinson's disease (PD) with typical Lewy-body pathology (after synuclein alpha (SNCA) and leucine rich repeat kinase 2 (LRRK2)). The protein encoded by TMEM230 remains largely uncharacterized, but initial evidence points to roles in the trafficking of recycling vesicles, retromers, and endosomes, suggesting intriguing links to the pathways targeted by other PD-causing genes...
June 1, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28554874/free-cholesterol-accumulation-in-liver-sinusoidal-endothelial-cells-exacerbates-acetaminophen-hepatotoxicity-via-tlr9-signaling
#13
Toshiaki Teratani, Kengo Tomita, Takahiro Suzuki, Hirotaka Furuhashi, Rie Irie, Shigeaki Hida, Yoshikiyo Okada, Chie Kurihara, Hirotoshi Ebinuma, Nobuhiro Nakamoto, Hidetsugu Saito, Toshifumi Hibi, Soichiro Miura, Ryota Hokari, Takanori Kanai
BACKGROUND & AIMS: Although obesity is a risk factor for acute liver failure, the pathogenic mechanisms are not yet fully understood. High cholesterol (HC) intake, which often underlies obesity, is suggested to play a role in the mechanism. We aimed to elucidate the effect of HC diet on acetaminophen-induced acute liver injury, the most frequent cause of acute liver failure in the USA. METHODS: C57BL/6 Toll-like receptor 9 (TLR9) knockout (Tlr9(-/-)) mice and their Tlr9(+/+) littermates were fed an HC diet for 4 weeks and then treated with acetaminophen...
May 26, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28550115/involvement-of-cell-surface-90-kda-heat-shock-protein-hsp90-in-pattern-recognition-by-human-monocyte-derived-macrophages
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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