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https://www.readbyqxmd.com/read/28910396/pi3k-c2%C3%AE-knockdown-decreases-autophagy-and-maturation-of-endocytic-vesicles
#1
Nathan M Merrill, Joshua L Schipper, Jonathan B Karnes, Audra L Kauffman, Katie R Martin, Jeffrey P MacKeigan
Phosphoinositide 3-kinase (PI3K) family members are involved in diverse cellular fates including cell growth, proliferation, and survival. While many molecular details are known about the Class I and III PI3Ks, less is known about the Class II PI3Ks. To explore the function of all eight PI3K isoforms in autophagy, we knock down each gene individually and measure autophagy. We find a significant decrease in autophagy following siRNA-mediated PIK3C2A (encoding the Class 2 PI3K, PI3K-C2α) knockdown. This defective autophagy is rescued by exogenous PI3K-C2α, but not kinase-dead PI3K-C2α...
2017: PloS One
https://www.readbyqxmd.com/read/28902870/reduced%C3%A2-insulin-signaling-maintains-electrical-transmission-in-a-neural-circuit-in-aging-flies
#2
Hrvoje Augustin, Kieran McGourty, Marcus J Allen, Sirisha Kudumala Madem, Jennifer Adcott, Fiona Kerr, Chi Tung Wong, Alec Vincent, Tanja Godenschwege, Emmanuel Boucrot, Linda Partridge
Lowered insulin/insulin-like growth factor (IGF) signaling (IIS) can extend healthy lifespan in worms, flies, and mice, but it can also have adverse effects (the "insulin paradox"). Chronic, moderately lowered IIS rescues age-related decline in neurotransmission through the Drosophila giant fiber system (GFS), a simple escape response neuronal circuit, by increasing targeting of the gap junctional protein innexin shaking-B to gap junctions (GJs). Endosomal recycling of GJs was also stimulated in cultured human cells when IIS was reduced...
September 2017: PLoS Biology
https://www.readbyqxmd.com/read/28874464/mas1-receptor-trafficking-involves-erk1-2-activation-through-a-%C3%AE-arrestin2-dependent-pathway
#3
Flavia M Cerniello, Oscar A Carretero, Nadia A Longo Carbajosa, Bruno D Cerrato, Robson A Santos, Hernán E Grecco, Mariela M Gironacci
The MAS1 receptor (R) exerts protective effects in the brain, heart, vessels, and kidney. R trafficking plays a critical function in signal termination and propagation and in R resensitization. We examined MAS1R internalization and trafficking on agonist stimulation and the role of β-arrestin2 in the activation of ERK1/2 (extracellular signal-regulated kinase 1/2) and Akt after MAS1R stimulation. Human embryonic kidney 293T cells were transfected with the coding sequence for MAS1R-YFP (MAS1R fused to yellow fluorescent protein)...
September 5, 2017: Hypertension
https://www.readbyqxmd.com/read/28857357/aspergillus-nidulans-baph-is-a-rab11-effector-that-connects-membranes-in-the-spitzenk%C3%A3-rper-with-basal-autophagy
#4
Mario Pinar, Miguel A Peñalva
Using affinity chromatography we identified the Aspergillus nidulans F-BAR-and-PH domain-containing protein BapH as a RabE(RAB11) effector. BapH localizes to the Spitzenkörper (SPK) in an F-actin- and Sec7-dependent manner, becoming cytosolic after inactivation of Trs120 in TRAPPII, the oligomeric GEF for RabE(RAB11) . Therefore RabE(RAB11) contributes to the recruitment of BapH to secretory vesicles in vivo. BapH has a close homologue, SlmA, which is related to yeast Slm1p/Slm2p, localizes to eisosomes and does not bind RabE(RAB11) ...
August 30, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28829741/selective-rab11-transport-and-the-intrinsic-regenerative-ability-of-cns-axons
#5
Hiroaki Koseki, Matteo Donegá, Brian Yh Lam, Veselina Petrova, Susan van Erp, Giles Sh Yeo, Jessica Cf Kwok, Charles Ffrench-Constant, RIchard Eva, James W Fawcett
Neurons lose intrinsic axon regenerative ability with maturation, but the mechanism remains unclear. Using an in-vitro laser axotomy model, we show a progressive decline in the ability of cut CNS axons to form a new growth cone and then elongate. Failure of regeneration was associated with increased retraction after axotomy. Transportation into axons becomes selective with maturation; we hypothesized that selective exclusion of molecules needed for growth may contribute to regeneration decline. With neuronal maturity Rab11 vesicles (which carry many molecules involved in axon growth) became selectively targeted to the somatodendritic compartment and excluded from axons...
August 8, 2017: ELife
https://www.readbyqxmd.com/read/28739266/identification-of-%C3%AE-helix-4-%C3%AE-4-of-rab11a-as-a-novel-rab11-binding-domain-rbd-interaction-of-rab11a-with-the-prostacyclin-receptor
#6
Eamon P Mulvaney, Fergal O'Meara, Amir R Khan, David J O'Connell, B Therese Kinsella
The cellular trafficking of numerous G protein-coupled receptors (GPCRs) is known to be regulated by Rab proteins that involves a direct protein:protein interaction between the receptor and the GTPase. In the case of the human prostacyclin receptor (hIP), it undergoes agonist-induced internalization and subsequent Rab11a-dependent recyclization involving an interaction between a Rab11-binding domain (RBD) localized within its carboxyl-tail domain with Rab11a. However, the GPCR-interacting domain on Rab11a itself is unknown...
July 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28732201/small-molecules-for-early-endosome-specific-patch-clamping
#7
Cheng-Chang Chen, Elisabeth S Butz, Yu-Kai Chao, Yulia Grishchuk, Lars Becker, Stefan Heller, Susan A Slaugenhaupt, Martin Biel, Christian Wahl-Schott, Christian Grimm
To resolve the subcellular distribution of endolysosomal ion channels, we have established a novel experimental approach to selectively patch clamp Rab5 positive early endosomes (EE) versus Rab7/LAMP1-positive late endosomes/lysosomes (LE/LY). To functionally characterize ion channels in endolysosomal membranes with the patch-clamp technique, it is important to develop techniques to selectively enlarge the respective organelles. We found here that two small molecules, wortmannin and latrunculin B, enlarge Rab5-positive EE when combined but not Rab7-, LAMP1-, or Rab11 (RE)-positive vesicles...
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28724764/rab5-and-rab11-are-required-for-clathrin-dependent-endocytosis-of-japanese-encephalitis-virus-in-bhk-21-cells
#8
Chun-Chun Liu, Yun-Na Zhang, Zhao-Yao Li, Jin-Xiu Hou, Jing Zhou, Lin Kan, Bin Zhou, Pu-Yan Chen
During infection Japanese Encephalitis Virus generally enters host cells via receptor-mediated clathrin dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and post-internalization of JEV were analyzed using biochemical inhibitors, RNA interference and dominant negative mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol, but not caveolae or macropinocytosis...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724758/the-shcd-phosphotyrosine-adaptor-subverts-canonical-egf-receptor-trafficking
#9
Melanie K B Wills, Hayley R Lau, Nina Jones
Shc family signalling adaptors connect activated transmembrane receptors to proximal effectors, and most also contain a sequence involved in clathrin-mediated receptor endocytosis. Notably, this AP2 adaptin binding motif (AD) is absent from the ShcD homolog, which also uniquely promotes ligand-independent phosphorylation of the Epidermal Growth Factor (EGF) Receptor (EGFR). We now report that cultured cells expressing ShcD exhibit reduced EGF uptake, commensurate with a decrease in EGFR surface presentation...
July 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28720835/exophagy-of-annexin-a2-via-rab11-rab8a-and-rab27a-in-ifn-%C3%AE-stimulated-lung-epithelial-cells
#10
Ying-Da Chen, Yi-Ting Fang, Yi-Lin Cheng, Chiou-Feng Lin, Li-Jin Hsu, Shu-Ying Wang, Robert Anderson, Chih-Peng Chang, Yee-Shin Lin
Annexin A2 (ANXA2), a phospholipid-binding protein, has multiple biological functions depending on its cellular localization. We previously demonstrated that IFN-γ-triggered ANXA2 secretion is associated with exosomal release. Here, we show that IFN-γ-induced autophagy is essential for the extracellular secretion of ANXA2 in lung epithelial cells. We observed colocalization of ANXA2-containing autophagosomes with multivesicular bodies (MVBs) after IFN-γ stimulation, followed by exosomal release. IFN-γ-induced exophagic release of ANXA2 could not be observed in ATG5-silenced or mutant RAB11-expressing cells...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28679631/myosin-independent-cytokinesis-in-giardia-utilizes-flagella-to-coordinate-force-generation-and-direct-membrane-trafficking
#11
William R Hardin, Renyu Li, Jason Xu, Andrew M Shelton, Germain C M Alas, Vladimir N Minin, Alexander R Paredez
Devoid of all known canonical actin-binding proteins, the prevalent parasite Giardia lamblia uses an alternative mechanism for cytokinesis. Unique aspects of this mechanism can potentially be leveraged for therapeutic development. Here, live-cell imaging methods were developed for Giardia to establish division kinetics and the core division machinery. Surprisingly, Giardia cytokinesis occurred with a median time that is ∼60 times faster than mammalian cells. In contrast to cells that use a contractile ring, actin was not concentrated in the furrow and was not directly required for furrow progression...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28674181/lung-epithelial-cell-derived-microvesicles-regulate-macrophage-migration-via-microrna-17-221-induced-integrin-%C3%AE-1-recycling
#12
Heedoo Lee, Duo Zhang, Jingxuan Wu, Leo E Otterbein, Yang Jin
Robust lung inflammation is one of the prominent features in the pathogenesis of acute lung injury (ALI). Macrophage migration and recruitment are often seen at the early stage of lung inflammatory responses to noxious stimuli. Using an acid inhalation-induced lung injury model, we explored the mechanisms by which acid exposure initiates macrophage recruitment and migration during development of ALI. The lung epithelium comprises a large surface area and functions as a first-line defense against noxious insults...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28654184/recycling-of-glucagon-receptor-to-plasma-membrane-increases-in-adipocytes-of-obese-rats-by-soy-protein-implications-for-glucagon-resistance
#13
Laura A Velázquez-Villegas, Claudia Tovar-Palacio, Berenice Palacios-González, Nimbe Torres, Armando R Tovar, Andrea Díaz-Villaseñor
SCOPE: Hyperglucagonemia contributes to hyperglycemia in type 2 diabetes (T2D). Previously, we have found that soy protein normalized fasting hyperglucagonemia in obese Zucker (fa/fa) rats, sensitizing the HSL-lipolytic signaling pathway in white adipose tissue (WAT), however the mechanism remains unknown. METHODS AND RESULTS: Zucker (fa/fa) rats were fed casein or soy protein diet in combination with soybean or coconut oil. Glucagon receptor (GR) was increased at the plasma membrane of adipocytes of rats fed soy protein compared to those fed casein, without changes in total GR abundance...
June 27, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28553202/a-systematic-rnai-screen-reveals-a-novel-role-of-a-spindle-assembly-checkpoint-protein-bugz-in-synaptic-transmission-in-c-elegans
#14
Mei Han, Wenjuan Zou, Hao Chang, Yong Yu, Haining Zhang, Shitian Li, Hankui Cheng, Guifeng Wei, Yan Chen, Valerie Reinke, Tao Xu, Lijun Kang
Synaptic vesicles (SV) store various neurotransmitters that are released at the synapse. The molecular mechanisms of biogenesis, exocytosis, and endocytosis for SV, however, remain largely elusive. In this study, using Complex Object Parametric Analysis and Sorter (COPAS) to monitor the fluorescence of synapto-pHluorin (SpH), we performed a whole-genome RNAi screen in C. elegans to identify novel genetic modulators in SV cycling. One hundred seventy six genes that up-regulating SpH fluorescence and 96 genes that down-regulating SpH fluorescence were identified after multi-round screen...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28527895/suppression-of-pmrab11-inhibits-yhv-infection-in-penaeus-monodon
#15
Akechai Kongprajug, Sakol Panyim, Chalermporn Ongvarrasopone
Yellow head virus (YHV) is one of the most serious pathogens that causes worldwide shrimp production loss. It enters the cells via clathrin-mediated endocytosis and utilizes small GTPase Rab proteins such as PmRab5 and PmRab7 for intracellular trafficking. In this study, molecular cloning and functional analysis of Rab11 during YHV infection were investigated. PmRab11 cDNA was cloned by Rapid amplification of cDNA ends (RACEs). It contained two forms of sizes 1200 and 1050 bp distinct at the 5' UTR. The coding region of PmRab11 was 645 bp, encoding 214 amino acids...
May 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28495999/%C3%AE-arrestin-mediated-regulation-of-the-human-ether-a-go-go-related-gene-potassium-channel
#16
Matthew G Sangoi, Shawn M Lamothe, Jun Guo, Tonghua Yang, Wentao Li, Ellen G Avery, John T Fisher, Shetuan Zhang
The rapidly activating delayed rectifier K(+) channel (IKr) is encoded by the human ether-a-go-go-related gene (hERG), which is important for the repolarization of the cardiac action potential. Mutations in hERG or drugs can impair the function or decrease the expression level of hERG channels, leading to long QT syndrome. Thus, it is important to understand hERG channel trafficking and its regulation. For this purpose, G protein-coupled receptors (GPCRs), which regulate a vast array of cellular processes, represent a useful route...
August 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28489965/evidence-for-the-subsynaptic-zone-as-a-preferential-site-for-chrn-recycling-at-neuromuscular-junctions
#17
Franziska Wild, Muzamil Majid Khan, Rüdiger Rudolf
Vertebrate skeletal muscle contraction is mediated by nicotinic acetylcholine receptors (CHRN). Endocytosis and recycling of CHRN regulate their proper abundance at nerve-muscle synapses, i.e. neuromuscular junctions. Recent work showed that RAB5 is essential for CHRN endocytosis. Here, using in vivo-imaging of endocytosed CHRN and RAB-GFP fusion proteins, we deliver evidence for differential effects of RAB5-GFP, RAB4-GFP, and RAB11-GFP on CHRN endocytosis. Furthermore, while newly endocytosed CHRN colocalized with RAB5-GFP over large stretches of muscle fibers, RAB4-GFP and RAB11-GFP colocalized with endocytosed CHRN almost exclusively at neuromuscular junctions...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28482024/vps35-in-cooperation-with-lrrk2-regulates-synaptic-vesicle-endocytosis-through-the-endosomal-pathway-in-drosophila
#18
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...
August 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28468881/mutations-in-the-transmembrane-domain-and-cytoplasmic-tail-of-hendra-virus-fusion-protein-disrupt-virus-like-particle-assembly
#19
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 endosomal F trafficking affects HeV assembly. We found that the HeV matrix (M) and F proteins each induced particle release when they were expressed alone but that their coexpression led to coordinated assembly of virus-like particles (VLPs) that were morphologically and physically distinct from M-only or F-only VLPs...
July 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28465352/cystinosin-the-small-gtpase-rab11-and-the-rab7-effector-rilp-regulate-intracellular-trafficking-of-the-chaperone-mediated-autophagy-receptor-lamp2a
#20
Jinzhong Zhang, Jennifer L Johnson, Jing He, Gennaro Napolitano, Mahalakshmi Ramadass, Celine Rocca, William B Kiosses, Cecilia Bucci, Qisheng Xin, Evripidis Gavathiotis, Ana María Cuervo, Stephanie Cherqui, Sergio D Catz
The lysosomal storage disease cystinosis, caused by cystinosin deficiency, is characterized by cell malfunction, tissue failure, and progressive renal injury despite cystine-depletion therapies. Cystinosis is associated with defects in chaperone-mediated autophagy (CMA), but the molecular mechanisms are incompletely understood. Here, we show CMA substrate accumulation in cystinotic kidney proximal tubule cells. We also found mislocalization of the CMA lysosomal receptor LAMP2A and impaired substrate translocation into the lysosome caused by defective CMA in cystinosis...
June 23, 2017: Journal of Biological Chemistry
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