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Recycling endosome

Jiejie Wang, Xinyou Lv, Yu Wu, Tao Xu, Mingfei Jiao, Risheng Yang, Xia Li, Ming Chen, Yinggang Yan, Changwan Chen, Weifan Dong, Wei Yang, Min Zhuo, Tao Chen, Jianhong Luo, Shuang Qiu
NMDA receptors (NMDARs) are crucial for excitatory synaptic transmission and synaptic plasticity. The number and subunit composition of synaptic NMDARs are tightly controlled by neuronal activity and sensory experience, but the molecular mechanism mediating NMDAR trafficking remains poorly understood. Here, we report that RIM1, with a well-established role in presynaptic vesicle release, also localizes postsynaptically in the mouse hippocampus. Postsynaptic RIM1 in hippocampal CA1 region is required for basal NMDAR-, but not AMPA receptor (AMPAR)-, mediated synaptic responses, and contributes to synaptic plasticity and hippocampus-dependent memory...
June 11, 2018: Nature Communications
Ewan MacDonald, Louise Brown, Arnaud Selvais, Han Liu, Thomas Waring, Daniel Newman, Jessica Bithell, Douglas Grimes, Sylvie Urbé, Michael J Clague, Tobias Zech
Transmembrane proteins in the sorting endosome are either recycled to their point of origin or destined for lysosomal degradation. Lysosomal sorting is mediated by interaction of ubiquitylated transmembrane proteins with the endosomal sorting complex required for transport (ESCRT) machinery. In this study, we uncover an alternative role for the ESCRT-0 component hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) in promoting the constitutive recycling of transmembrane proteins. We find that endosomal localization of the actin nucleating factor Wiscott-Aldrich syndrome protein and SCAR homologue (WASH) requires HRS, which occupies adjacent endosomal subdomains...
June 11, 2018: Journal of Cell Biology
Akram Zamani, Junhua Xiao, Ann M Turnley, Simon S Murray
Brain-derived neurotrophic factor (BDNF) is highly expressed in the hippocampus, where it can initiate signalling pathways leading to neurite outgrowth, neuron survival, spine maturation and increased synapse strength. Although suppressor of cytokine signalling 2 (SOCS2) is primarily known to negatively regulate cytokine signalling, it is also highly expressed in the hippocampus and exerts neuron-specific functions in the brain, effecting the length and architecture of neurons. However, little is known about the role of SOCS2 in the hippocampus...
June 7, 2018: Molecular Neurobiology
Kunihiko Kanatsu, Yukiko Hori, Ihori Ebinuma, Yung Wen Chiu, Taisuke Tomita
The aberrant metabolism of amyloid-β protein (Aβ) in the human brain has been implicated in the etiology of Alzheimer disease (AD). γ-Secretase is the enzyme that generates various forms of Aβ, such as Aβ40 and Aβ42, the latter being an aggregation-prone toxic peptide that is involved in the pathogenesis of AD. Recently, we found that clathrin-mediated endocytosis of γ-secretase affects the production and deposition of Aβ42 in vivo, suggesting that the membrane trafficking of γ-secretase affects its enzymatic activity...
May 31, 2018: Journal of Neurochemistry
Mohammed M Nooh, Salvatore Mancarella, Suleiman W Bahouth
The β1 -adrenergic receptor (β1 -AR) is a major cardiac G protein-coupled receptor, which mediates cardiac actions of catecholamines and is involved in genesis and treatment of numerous cardiovascular disorders. In mammalian cells, catecholamines induce the internalization of the β1 -AR into endosomes and their removal promotes the recycling of endosomal β1 -AR back to the plasma membrane, but whether these redistributive processes occur in terminally differentiated cells is unknown. Compartmentalization of the β1 -AR in response to β-agonists and antagonists was determined by confocal microscopy in primary adult rat ventricular myocytes (ARVM), which are terminally differentiated myocytes with unique structures such as t-tubules and contractile sarcomeres...
May 30, 2018: Molecular Pharmacology
Brendan T Finicle, Manuel U Ramirez, Gang Liu, Elizabeth M Selwan, Alison N McCracken, Jingwen Yu, Yoosun Joo, Jannett Nguyen, Kevin Ou, Saurabh Ghosh Roy, Victor D Mendoza, Dania Virginia Corrales, Aimee L Edinger
Endogenous sphingolipids (ceramide) and related synthetic molecules (FTY720, SH-BC-893) reduce nutrient access by decreasing cell surface expression of a subset of nutrient transporter proteins. Here, we report that these sphingolipids disrupt endocytic recycling by inactivating the small GTPase ARF6. Consistent with reported roles for ARF6 in maintaining the tubular recycling endosome, MICAL-L1-positive tubules were lost from sphingolipid-treated cells. ARF6 inactivation may occur downstream of PP2A activation...
May 30, 2018: Journal of Cell Science
Kira V Gromova, Mary Muhia, Nicola Rothammer, Christine E Gee, Edda Thies, Irina Schaefer, Sabrina Kress, Manfred W Kilimann, Olga Shevchuk, Thomas G Oertner, Matthias Kneussel
Autism spectrum disorders (ASDs) are associated with mutations affecting synaptic components, including GluN2B-NMDA receptors (NMDARs) and neurobeachin (NBEA). NBEA participates in biosynthetic pathways to regulate synapse receptor targeting, synaptic function, cognition, and social behavior. However, the role of NBEA-mediated transport in specific trafficking routes is unclear. Here, we highlight an additional function for NBEA in the local delivery and surface re-insertion of synaptic receptors in mouse neurons...
May 29, 2018: Cell Reports
Keith Ireton, Hoan Van Ngo, Manmeet Bhalla
Many microbial pathogens co-opt or pertub host membrane trafficking pathways. This review covers recent examples in which microbes interact with host exocytosis, the fusion of intracellular vesicles with the plasma membrane. The bacterial pathogens Listeria monocytogenes and Staphylococcus aureus subvert recycling endosomal pathways of exocytosis in order to induce their entry into human cells. By contrast, entry of the protozoan pathogen Trypanosoma cruzi or the virus adenovirus into host cells involves exploitation of lysosomal exocytosis...
May 24, 2018: Cellular Microbiology
M Chincholkar
The focus of perioperative pain management should be to attempt to minimise the nociceptive input and reduce the risk of transition to central sensitisation. Gabapentinoids are being increasingly used as adjuncts for management of perioperative pain. Although gabapentinoids are classed as calcium channel blockers, their mechanisms of action are poorly understood. The analgesic effect in neuropathic pain is well evidenced but the role in postoperative pain is less certain. Medline and EMBASE database searches were conducted to identify studies relating to mechanisms of action and effects in experimental animal models of inflammatory and postoperative pain and human models of experimental pain...
June 2018: British Journal of Anaesthesia
Matthew N J Seaman, Aamir S Mukadam, Sophia Y Breusegem
The retromer complex is a vital component of the endosomal protein sorting machinery being necessary for sorting into both the endosome-to-Golgi retrieval pathway and also the endosome-to-cell-surface recycling pathway. Retromer mediates cargo selection through a trimeric complex comprising VPS35, VPS29 and VPS26 which is recruited to endosomes by binding to Rab7a and Snx3. Retromer function is linked to two distinct neurodegenerative diseases, Parkinson's disease and Alzheimer's disease and modulating retromer function has been proposed as an avenue to explore for a putative therapy in these conditions...
May 18, 2018: Journal of Cell Science
Manveen K Gupta, Maradumane L Mohan, Sathyamangla V Naga Prasad
Cellular responses to extracellular milieu/environment are driven by cell surface receptors that transmit the signal into the cells resulting in a synchronized and measured response. The ability to provide such exquisite responses to changes in external environment is mediated by the tight and yet, deliberate regulation of cell surface receptor function. In this regard, the seven transmembrane G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors that regulate responses like cardiac contractility, vision, and olfaction including platelet activation...
2018: International Review of Cell and Molecular Biology
Yun-Na Zhang, Ya-Yun Liu, Fu-Chuan Xiao, Chun-Chun Liu, Xiao-Dong Liang, Jing Chen, Jing Zhou, Abdul Sattar Baloch, Lin Kan, Bin Zhou, Hua-Ji Qiu
The members of Flaviviridae utilize several endocytic pathways to enter a variety of host cells. Our previous work showed that classical swine fever virus (CSFV) enters porcine kidney (PK-15) cells through a clathrin-dependent pathway that requires Rab5 and Rab7. The entry mechanism for CSFV into other cell lines remains unclear, for instance, porcine alveolar macrophages (3D4/21 cells). More importantly, the trafficking of CSFV within endosomes controlled by Rab GTPases is unknown in 3D4/21 cells. In this study, entry and post-internalization of CSFV were analyzed using chemical inhibitors, RNA interference, and dominant negative (DN) mutants...
May 16, 2018: Journal of Virology
Claudia A Bertuccio, Tony T Wang, Kirk L Hamilton, Diego J Rodriguez-Gil, Steven B Condliffe, Daniel C Devor
We previously demonstrated endocytosis of KCa2.3 is caveolin-1-, dynamin II- and Rab5-dependent. KCa2.3 then enters Rab35/EPI64C- and RME-1-containing recycling endosomes and is returned to the plasma membrane (PM). Herein, we report on the mechanism by which KCa2.3 is inserted into the PM during recycling and following exit from the Golgi. We demonstrate KCa2.3 colocalizes with SNAP-23 and Syntaxin-4 in the PM of HEK and endothelial cells by confocal immunofluorescence microscopy. We further show KCa2.3 can be co-immunoprecipitated with SNAP-23 and Syntaxin-4...
2018: PloS One
Samual C Allgood, M Ramona Neunuebel
Bacterial pathogens have developed a wide range of strategies to survive within human cells. A number of pathogens multiply in a vacuolar compartment, while others can rupture the vacuole and replicate in the host cytosol. A common theme among many bacterial pathogens is the use of specialized secretion systems to deliver effector proteins into the host cell. These effectors can manipulate the host's membrane trafficking pathways to remodel the vacuole into a replication-permissive niche and prevent degradation...
May 10, 2018: Cellular Microbiology
Gulpreet Kaur, Aparna Lakkaraju
Early endosomes are organelles that receive macromolecules and solutes from the extracellular environment. The major function of early endosomes is to sort these cargos into recycling and degradative compartments of the cell. Degradation of the cargo involves maturation of early endosomes into late endosomes, which, after acquisition of hydrolytic enzymes, form lysosomes. Endosome maturation involves recruitment of specific proteins and lipids to the early endosomal membrane, which drives changes in endosome morphology...
2018: Advances in Experimental Medicine and Biology
Basant A Abdulrahman, Dalia H Abdelaziz, Hermann M Schatzl
Prions are protein-based infectious agents that autocatalytically convert the cellular prion protein PrPC to its pathological isoform PrPSc Subsequent aggregation and accumulation of PrPSc in nervous tissues causes several invariably fatal neurodegenerative diseases in humans and animals. Prions can infect recipient cells when packaged into endosome-derived nanoparticles called exosomes, which are present in biological fluids such as blood, urine, and saliva. Autophagy is a basic cellular degradation and recycling machinery that also affects exosomal processing, but whether autophagy controls release of prions in exosomes is unclear...
April 26, 2018: Journal of Biological Chemistry
Francesco De Pascali, Aurélie Tréfier, Flavie Landomiel, Véronique Bozon, Gilles Bruneau, Romain Yvinec, Anne Poupon, Pascale Crépieux, Eric Reiter
Follicle-stimulating hormone (FSH) is produced in the pituitary and is essential for reproduction. It specifically binds to a membrane receptor (FSHR) expressed in somatic cells of the gonads. The FSH/FSHR system presents many peculiarities compared to classical G protein-coupled receptors (GPCRs). FSH is a large naturally heterogeneous heterodimeric glycoprotein. The FSHR is characterized by a very large NH2-terminal extracellular domain, which binds FSH and participates to the activation/inactivation switch of the receptor...
2018: International Review of Cell and Molecular Biology
Ewoud B Compeer, Felix Kraus, Manuela Ecker, Gregory Redpath, Mayan Amiezer, Nils Rother, Philip R Nicovich, Natasha Kapoor-Kaushik, Qiji Deng, Guerric P B Samson, Zhengmin Yang, Jieqiong Lou, Michael Carnell, Haig Vartoukian, Katharina Gaus, Jérémie Rossy
Endocytosis of surface receptors and their polarized recycling back to the plasma membrane are central to many cellular processes, such as cell migration, cytokinesis, basolateral polarity of epithelial cells and T cell activation. Little is known about the mechanisms that control the organization of recycling endosomes and how they connect to receptor endocytosis. Here, we follow the endocytic journey of the T cell receptor (TCR), from internalization at the plasma membrane to recycling back to the immunological synapse...
April 23, 2018: Nature Communications
Wenhui Zheng, Yahong Lin, Wenqin Fang, Xu Zhao, Yi Lou, Guanghui Wang, Huawei Zheng, Qifu Liang, Yakubu Saddeeq Abubakar, Stefan Olsson, Jie Zhou, Zonghua Wang
Endosomal sorting machineries regulate the transport of their cargoes among intracellular compartments. However, the molecular nature of such intracellular trafficking processes in pathogenic fungal development and pathogenicity remains unclear. Here, we dissect the roles and molecular mechanisms of two sorting nexin proteins and their cargoes in endosomal recycling in Fusarium graminearum using high-resolution microscopy and high-throughput co-immunoprecipitation strategies. We show that the sorting nexins, FgSnx41 and FgSnx4, interact with each other and assemble into a functionally interdependent heterodimer through their respective BAR domains...
April 20, 2018: New Phytologist
Heather E Miller, Charles L Larson, Robert A Heinzen
Coxiella burnetii is an intracellular bacterium that replicates within an expansive phagolysosome-like vacuole. Fusion between the Coxiella-containing vacuole (CCV) and late endosomes/multivesicular bodies requires Rab7, the HOPS tethering complex, and SNARE proteins, with actin also speculated to play a role. Here, we investigated the importance of actin in CCV fusion. Filamentous actin patches formed around the CCV membrane that were preferred sites of vesicular fusion. Accordingly, the mediators of endolysosomal fusion Rab7, VAMP7, and syntaxin 8 were concentrated in CCV actin patches...
April 2018: PLoS Pathogens
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