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Endosomal trafficking

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https://www.readbyqxmd.com/read/28544880/systems-wide-studies-uncover-commander-a-multiprotein-complex-essential-to-human-development
#1
REVIEW
Anna L Mallam, Edward M Marcotte
Recent mass spectrometry maps of the human interactome independently support the existence of a large multiprotein complex, dubbed "Commander." Broadly conserved across animals and ubiquitously expressed in nearly every human cell type examined thus far, Commander likely plays a fundamental cellular function, akin to other ubiquitous machines involved in expression, proteostasis, and trafficking. Experiments on individual subunits support roles in endosomal protein sorting, including the trafficking of Notch proteins, copper transporters, and lipoprotein receptors...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28533468/vacuolation-activity-and-intracellular-trafficking-of-artb-the-binding-subunit-of-an-ab5-toxin-produced-by-salmonella-enterica-serovar-typhi
#2
Brock P Herdman, James C Paton, Hui Wang, Travis Beddoe, Adrienne W Paton
Various Salmonella enterica serovars, including S Typhi, encode an AB5 toxin (ArtAB), the A subunit of which is an ADP-ribosyltransferase related to the S1 subunit of pertussis toxin. However, although the A subunit is able to catalyse ADP-ribosylation of host G proteins, a cytotoxic phenotype has yet to be identified for the holotoxin. Here we show that its B subunit pentamer (ArtB) binds to receptors on the surface of Vero (African green monkey kidney), CHO (Chinese hamster ovary), U937 (human monocyte) and HBMEC (human brain microvascular endothelial) cell lines...
May 22, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28533221/cd9-regulates-mhc-ii-trafficking-in-monocyte-derived-dendritic-cells
#3
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/28526875/endophilinas-regulate-endosomal-sorting-of-bdnf-trkb-to-mediate-survival-signaling-in-hippocampal-neurons
#4
Katja Burk, John D Murdoch, Siona Freytag, Melanie Koenig, Vinita Bharat, Ronja Markworth, Susanne Burkhardt, Andre Fischer, Camin Dean
The sorting of activated receptors into distinct endosomal compartments is essential to activate specific signaling cascades and cellular events including growth and survival. However, the proteins involved in this sorting are not well understood. We discovered a novel role of EndophilinAs in sorting of activated BDNF-TrkB receptors into late endosomal compartments. Mice lacking all three EndophilinAs accumulate Rab7-positive late endosomes. Moreover, EndophilinAs are differentially localized to, co-traffic with, and tubulate, distinct endosomal compartments: In response to BDNF, EndophilinA2 is recruited to both early and late endosomes, EndophilinA3 is recruited to Lamp1-positive late endosomes, and co-trafficks with Rab5 and Rab7 in both the presence and absence of BDNF, while EndophilinA1 colocalizes at lower levels with endosomes...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522593/small-gtpase-rab1b-is-associated-with-atg9a-vesicles-and-regulates-autophagosome-formation
#5
Soichiro Kakuta, Junji Yamaguchi, Chigure Suzuki, Mitsuho Sasaki, Saiko Kazuno, Yasuo Uchiyama
ATG9 is a membrane protein that is essential for autophagy and is considered to be directly involved in the early steps of autophagosome formation. Yeast Atg9 is mainly localized to small vesicles (Atg9 vesicles), whereas mammalian ATG9A is reportedly localized to the trans-Golgi network, the endosomal compartment, and other unidentified membrane structures. To dissect the ATG9A-containing membranes, we examined the subcellular localization of ATG9A and performed immunoisolation of those membranes. ATG9A-green fluorescent protein in human culture cells was observed as numerous puncta that move rapidly throughout the cytoplasm...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28514713/pattern-recognition-receptors-and-coordinated-cellular-pathways-involved-in-tuberculosis-immunopathogenesis-emerging-concepts-and-perspectives
#6
REVIEW
Abhishek Mishra, Shamim Akhtar, Chinnaswamy Jagannath, Arshad Khan
Pattern Recognition Receptors (PRRs) play a central role in the recognition of numerous pathogens, including Mycobacterium tuberculosis, resulting in activation of innate and adaptive immune responses. Besides Toll Like Receptors, C-type Lectin Receptors and Nod Like Receptors are now being recognized for their involvement in inducing immune response against M. tuberculosis infection. Although, a functional redundancy of the PRRs has also been reported in many studies, emerging evidences support the notion that a cooperative and coordinated response generated by these receptors is critical to sustain the full immune control of M...
May 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28507272/phosphatidylinositol-5-phosphate-4-kinase-regulates-early-endosomal-dynamics-during-clathrin-mediated-endocytosis
#7
Kumari Kamalesh, Deepti Trivedi, Sarah Toscano, Sanjeev Sharma, Sourav Kolay, Padinjat Raghu
Endocytic turnover is essential to regulate the protein composition and function of the plasma membrane thus regulating the plasma membrane levels of many receptors. In Drosophila photoreceptors, photon absorption by the GPCR rhodopsin 1 (Rh1) triggers its endocytosis by clathrin-mediated endocytosis (CME). We find that CME of Rh1 is regulated by phosphatidylinositol 5 phosphate 4-kinase (PIP4K). Flies lacking PIP4K show mislocalization of Rh1 on expanded endomembranes within the cell body. This mislocalization of Rh1 was dependent on the formation of an expanded Rab5 compartment...
May 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28504462/endocytic-activity-of-hiv-1-vpu-phosphoserine-dependent-interactions-with-clathrin-adaptors
#8
Charlotte A Stoneham, Rajendra Singh, Xiaofei Jia, Yong Xiong, John Guatelli
HIV-1 Vpu modulates cellular transmembrane proteins to optimize viral replication and provide immune-evasion, triggering ubiquitin-mediated degradation of some targets but also modulating endosomal trafficking to deplete them from the plasma membrane. Interactions between Vpu and the heterotetrameric clathrin adaptors AP-1 and AP-2 have been described, yet the molecular basis and functional roles of such interactions are incompletely defined. To investigate the trafficking signals encoded by Vpu, we fused the cytoplasmic domain (CD) of Vpu to the extracellular and transmembrane domains of the CD8 α-chain...
May 14, 2017: Traffic
https://www.readbyqxmd.com/read/28498820/lysosomal-regulation-of-cholesterol-homeostasis-in-tuberous-sclerosis-complex-is-mediated-via-npc1-and-ldl-r
#9
Harilaos Filippakis, Nicola Alesi, Barbara Ogorek, Julie Nijmeh, Damir Khabibullin, Catherine Gutierrez, Alexander J Valvezan, James Cunningham, Carmen Priolo, Elizabeth P Henske
Tuberous sclerosis complex (TSC) is a multisystem disease associated with hyperactive mTORC1. The impact of TSC1/2 deficiency on lysosome-mediated processes is not fully understood. We report here that inhibition of lysosomal function using chloroquine (CQ) upregulates cholesterol homeostasis genes in TSC2-deficient cells. This TSC2-dependent transcriptional signature is associated with increased accumulation and intracellular levels of both total cholesterol and cholesterol esters. Unexpectedly, engaging this CQ-induced cholesterol uptake pathway together with inhibition of de novo cholesterol synthesis allows survival of TSC2-deficient, but not TSC2-expressing cells...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498635/snx10-plays-a-critical-role-in-mmp9-secretion-via-jnk-p38-erk-signaling-pathway
#10
Chun Zhou, Ying Wang, Jin Peng, Cuixian Li, Peiqing Liu, Xiaoyan Shen
Matrix metalloproteinases (MMPs) plays a critical role in the degradation of extracellular matrix (ECM). Sorting nexin (SNX) 10 is a member of the SNX family, which functions in regulation of endosomal sorting and osteoclast activation, has been implicated to play an important role in the bone erosion of rheumatoid arthritis. In this study, we aimed to investigate the possible role of SNX10 on MMP9 secretion and the potential mechanism. By immunostaining and co-immunoprecipitation, we found that SNX10 was extensively co-localized with MMP9, indicating that SNX10 might participate in MMP9 trafficking...
May 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28494243/a-rab20-dependent-membrane-trafficking-pathway-controls-m-%C3%A2-tuberculosis-replication-by-regulating-phagosome-spaciousness-and-integrity
#11
Laura Schnettger, Angela Rodgers, Urska Repnik, Rachel P Lai, Gang Pei, Martijn Verdoes, Robert J Wilkinson, Douglas B Young, Maximiliano G Gutierrez
The intracellular pathogen Mycobacterium tuberculosis (Mtb) lives within phagosomes and also disrupts these organelles to access the cytosol. The host pathways and mechanisms that contribute to maintaining Mtb phagosome integrity have not been investigated. Here, we examined the spatiotemporal dynamics of Mtb-containing phagosomes and identified an interferon-gamma-stimulated and Rab20-dependent membrane trafficking pathway in macrophages that maintains Mtb in spacious proteolytic phagolysosomes. This pathway functions to promote endosomal membrane influx in infected macrophages, and is required to preserve Mtb phagosome integrity and control Mtb replication...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28487419/membrane-depolarization-activates-bk-channels-through-rock-mediated-%C3%AE-1-subunit-surface-trafficking-to-limit-vasoconstriction
#12
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/28482115/arabidopsis-thaliana-fla4-functions-as-a-glycan-stabilized-soluble-factor-via-its-carboxy-proximal-fasciclin-1-domain
#13
Hui Xue, Christiane Veit, Lindy Abas, Theodora Tryfona, Daniel Maresch, Martiniano M Ricardi, Jose M Estevez, Richard Strasser, Georg J Seifert
Fasciclin like arabinogalactan proteins (FLAs) are involved in numerous important functions in plants but the relevance of their complex structure to physiological function and cellular fate is unresolved. Using a fully functional fluorescent version of Arabidopsis thaliana FLA4 we show that this protein is localized at the plasma membrane as well as in endosomes and soluble in the apoplast. FLA4 is likely to be GPI-anchored, is highly N-glycosylated and carries two O-glycan epitopes previously associated with AGPs...
May 8, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28481347/membrane-curvature-regulates-ligand-specific-membrane-sorting-of-gpcrs-in-living-cells
#14
Kadla R Rosholm, Natascha Leijnse, Anna Mantsiou, Vadym Tkach, Søren L Pedersen, Volker F Wirth, Lene B Oddershede, Knud J Jensen, Karen L Martinez, Nikos S Hatzakis, Poul Martin Bendix, Andrew Callan-Jones, Dimitrios Stamou
The targeted spatial organization (sorting) of Gprotein-coupled receptors (GPCRs) is essential for their biological function and often takes place in highly curved membrane compartments such as filopodia, endocytic pits, trafficking vesicles or endosome tubules. However, the influence of geometrical membrane curvature on GPCR sorting remains unknown. Here we used fluorescence imaging to establish a quantitative correlation between membrane curvature and sorting of three prototypic class A GPCRs (the neuropeptide Y receptor Y2, the β1 adrenergic receptor and the β2 adrenergic receptor) in living cells...
May 8, 2017: Nature Chemical Biology
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
#15
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/28475030/characterizing-the-spatio-temporal-role-of-sorting-nexin-17-in-human-papillomavirus-trafficking
#16
Martina Bergant, Špela Peternel, David Pim, Justyna Broniarczyk, Lawrence Banks
The human papillomavirus (HPV) L2 capsid protein plays an essential role during the early stages of viral infection. Previous studies have shown that the interaction between HPV L2 and endosomal sorting nexin 17 (SNX17) is conserved across multiple PV types where it plays an essential role in infectious entry, suggesting an evolutionarily conserved pathway of PV trafficking. Here we show that the peak time of interaction between HPV-16 L2 and SNX17 is rather early, at 2 h post-infection. Interestingly, the L2-SNX17 interaction appears to be important for facilitating capsid disassembly and L1 dissociation, suggesting that L2 recruitment of SNX17 occurs prior to capsid disassembly...
April 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28468990/multiple-activities-of-arl1-gtpase-in-the-trans-golgi-network
#17
REVIEW
Chia-Jung Yu, Fang-Jen S Lee
ADP-ribosylation factors (Arfs) and ADP-ribosylation factor-like proteins (Arls) are highly conserved small GTPases that function as main regulators of vesicular trafficking and cytoskeletal reorganization. Arl1, the first identified member of the large Arl family, is an important regulator of Golgi complex structure and function in organisms ranging from yeast to mammals. Together with its effectors, Arl1 has been shown to be involved in several cellular processes, including endosomal trans-Golgi network and secretory trafficking, lipid droplet and salivary granule formation, innate immunity and neuronal development, stress tolerance, as well as the response of the unfolded protein...
May 3, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28468881/mutations-in-the-transmembrane-domain-and-cytoplasmic-tail-of-hendra-virus-fusion-protein-disrupt-virus-like-particle-assembly
#18
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/28467418/a-kcnc3-mutation-causes-a-neurodevelopmental-non-progressive-sca13-subtype-associated-with-dominant-negative-effects-and-aberrant-egfr-trafficking
#19
Swati Khare, Jerelyn A Nick, Yalan Zhang, Kira Galeano, Brittany Butler, Habibeh Khoshbouei, Sruti Rayaprolu, Tyisha Hathorn, Laura P W Ranum, Lisa Smithson, Todd E Golde, Martin Paucar, Richard Morse, Michael Raff, Julie Simon, Magnus Nordenskjöld, Karin Wirdefeldt, Diego E Rincon-Limas, Jada Lewis, Leonard K Kaczmarek, Pedro Fernandez-Funez, Harry S Nick, Michael F Waters
The autosomal dominant spinocerebellar ataxias (SCAs) are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3...
2017: PloS One
https://www.readbyqxmd.com/read/28464829/a-mechanistic-investigation-exploring-the-differential-transfection-efficiencies-between-the-easy-to-transfect-sk-br3-and-difficult-to-transfect-ct26-cell-lines
#20
Elizabeth Figueroa, Pallavi Bugga, Vishwaratn Asthana, Allen L Chen, J Stephen Yan, Emily Reiser Evans, Rebekah A Drezek
BACKGROUND: Gold-polyamidoamine (AuPAMAM) has previously been shown to successfully transfect cells with high efficiency. However, we have observed that certain cell types are more amenable to Au-PAMAM transfection than others. Here we utilized two representative cell lines-a "difficult to transfect" CT26 cell line and an "easy to transfect" SK-BR3 cell line-and attempted to determine the underlying mechanism for differential transfection in both cell types. Using a commonly established poly-cationic polymer similar to PAMAM (polyethyleneimine, or PEI), we additionally sought to quantify the relative transfection efficiencies of each vector in CT26 and SK-BR3 cells, in the hopes of elucidating any mechanistic differences that may exist between the two transfection vectors...
May 2, 2017: Journal of Nanobiotechnology
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