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Endocytic trafficking

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https://www.readbyqxmd.com/read/28640985/the-interaction-between-progranulin-and-prosaposin-is-mediated-by-granulins-and-the-linker-region-between-saposin-b-and-c
#1
Xiaolai Zhou, Peter M Sullivan, Lirong Sun, Fenghua Hu
The frontotemporal lobar degeneration (FTLD) protein progranulin (PGRN) is essential for proper lysosomal function. PGRN localizes in the lysosomal compartment within the cell. Prosaposin (PSAP), the precursor of lysosomal saposin activators (saposin A, B, C, D), physically interacts with PGRN. Previously we have shown that PGRN and PSAP facilitate each other's lysosomal trafficking. Here we report that the interaction between PSAP and PGRN requires the linker region of saposin B and C (BC linker). PSAP protein with the BC linker mutated fails to interact with PGRN and target PGRN to lysosomes in the biosynthetic and endocytic pathways...
June 22, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28634349/synuclein-impairs-trafficking-and-signaling-of-bdnf-in-a-mouse-model-of-parkinson-s-disease
#2
Fang Fang, Wanlin Yang, Jazmin B Florio, Edward Rockenstein, Brian Spencer, Xavier M Orain, Stephanie X Dong, Huayan Li, Xuqiao Chen, Kijung Sung, Robert A Rissman, Eliezer Masliah, Jianqing Ding, Chengbiao Wu
Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease. Using a transgenic mouse model of Parkinson's disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28632996/taking-control-hijacking-of-rab-gtpases-by-intracellular-bacterial-pathogens
#3
Stefania Spanò, Jorge E Galán
Intracellular bacterial pathogens survive and replicate within specialized eukaryotic cell organelles. To establish their intracellular niches these pathogens have adopted sophisticated strategies to control intracellular membrane trafficking. Since Rab-family GTPases are critical regulators of endocytic and secretory membrane trafficking events, many intracellular pathogens have evolved specific mechanisms to modulate or hijack Rab GTPases dynamics and trafficking functions. One such strategy is the delivery of bacterial effectors through specialized machines to specifically target Rab GTPases...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28592304/post-translational-changes-to-%C3%AE-synuclein-control-iron-and-dopamine-trafficking-a-concept-for-neuron-vulnerability-in-parkinson-s-disease
#4
REVIEW
James A Duce, Bruce X Wong, Hannah Durham, Jean-Christophe Devedjian, David P Smith, David Devos
Parkinson's disease is a multifactorial neurodegenerative disorder, the aetiology of which remains elusive. The primary clinical feature of progressively impaired motor control is caused by a loss of midbrain substantia nigra dopamine neurons that have a high α-synuclein (α-syn) and iron content. α-Syn is a neuronal protein that is highly modified post-translationally and central to the Lewy body neuropathology of the disease. This review provides an overview of findings on the role post translational modifications to α-syn have in membrane binding and intracellular vesicle trafficking...
June 7, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28591131/visualization-of-early-influenza-a-virus-trafficking-in-human-dendritic-cells-using-sted-microscopy
#5
Faezzah Baharom, Oliver S Thomas, Rico Lepzien, Ira Mellman, Cécile Chalouni, Anna Smed-Sörensen
Influenza A viruses (IAV) primarily target respiratory epithelial cells, but can also replicate in immune cells, including human dendritic cells (DCs). Super-resolution microscopy provides a novel method of visualizing viral trafficking by overcoming the resolution limit imposed by conventional light microscopy, without the laborious sample preparation of electron microscopy. Using three-color Stimulated Emission Depletion (STED) microscopy, we visualized input IAV nucleoprotein (NP), early and late endosomal compartments (EEA1 and LAMP1 respectively), and HLA-DR (DC membrane/cytosol) by immunofluorescence in human DCs...
2017: PloS One
https://www.readbyqxmd.com/read/28586196/real-time-imaging-of-endocytosis-and-intracellular-trafficking-of-semiconducting-polymer-dots
#6
Yuping Han, Xiaoming Li, Haobin Chen, Xingjie Hu, Yao Luo, Ting Wang, Zejun Wang, Qian Li, Chunhai Fan, Jiye Shi, Lihua Wang, Yun Zhao, Changfeng Wu, Nan Chen
Semiconducting polymer dots (Pdots) have shown great promise in biomedical applications, including biosensing, drug delivery, and live imaging of cells and biomolecules. Insight into the mechanism and regulation of cellular uptake and intracellular metabolism of Pdots is important for the development of superior Pdots-based theranostic nanoconjugates. Herein, we performed real-time imaging of endocytosis and intracellular trafficking of a type of fluorescent Pdots that showed excellent biocompatibility in various types of cells...
June 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28584820/the-ldl-receptor-related-protein-1-at-the-crossroads-of-lipoprotein-metabolism-and-insulin-signaling
#7
REVIEW
Dianaly T Au, Dudley K Strickland, Selen C Muratoglu
The metabolic syndrome is an escalating worldwide public health concern. Defined by a combination of physiological, metabolic, and biochemical factors, the metabolic syndrome is used as a clinical guideline to identify individuals with a higher risk for type 2 diabetes and cardiovascular disease. Although risk factors for type 2 diabetes and cardiovascular disease have been known for decades, the molecular mechanisms involved in the pathophysiology of these diseases and their interrelationship remain unclear...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28580168/caml-mediates-survival-of-myc-induced-lymphoma-cells-independent-of-tail-anchored-protein-insertion
#8
Jennifer C Shing, Lonn D Lindquist, Nica Borgese, Richard J Bram
Calcium-modulating cyclophilin ligand (CAML) is an endoplasmic reticulum (ER) protein that functions, along with WRB and TRC40, to mediate tail-anchored (TA) protein insertion into the ER membrane. Physiologic roles for CAML include endocytic trafficking, intracellular calcium signaling, and the survival and proliferation of specialized immune cells, recently attributed to its requirement for TA protein insertion. To identify a possible role for CAML in cancer cells, we generated Eμ-Myc transgenic mice that carry a tamoxifen-inducible deletion allele of Caml...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28577227/-search-for-risk-genes-in-alzheimer-s-disease
#9
REVIEW
I Karaca, H Wagner, A Ramirez
Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. The susceptibility to AD is determined by a complex interaction between genetic, epigenetic, and environmental factors. Herein, the risk that can be attributed to genetic factors is high (up to 80%). While most AD patients are sporadic, in rare families Mendelian mode of inheritance can be observed. In these rare familial cases, full penetrant mutations have been identified in APP, PSEN1, and PSEN2. Mutations in these three genes are however rarely found in sporadic AD...
June 2, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28573151/nervous-system-development-relies-on-endosomal-trafficking
#10
Ivan Mestres, Ching-Hwa Sung
Accumulating findings have begun to unveil the important role of the endosomal machinery in the nervous system development. Endosomes have been linked to the differential segregation of cell fate determining molecules in asymmetrically dividing progenitors during neurogenesis. Additionally, the precise removal and reinsertion of membrane components through endocytic trafficking regulates the spatial and temporal distribution of signaling receptors and adhesion molecules, which determine the morphology and motility of migrating neurons...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28566554/pi3k-class-ii-%C3%AE-regulates-%C3%AE-opioid-receptor-export-from-the-trans-golgi-network
#11
Daniel J Shiwarski, Marlena Darr, Cheryl A Telmer, Marcel P Bruchez, Manojkumar A Puthenveedu
The interplay between signaling and trafficking by G protein-coupled receptors (GPCRs) has focused mainly on endocytic trafficking. Whether and how surface delivery of newly synthesized GPCRs is regulated by extracellular signals is less understood. Here we define a signaling-regulated checkpoint at the trans-Golgi network (TGN) that controls the surface delivery of the delta opioid receptor (δR). In PC12 cells, inhibition of Phosphoinositide-3 Kinase (PI3K) activity blocked export of newly synthesized δR from the Golgi and delivery to the cell surface, similar to treatment with Nerve Growth Factor (NGF)...
May 31, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28550201/the-influence-of-mhc-class-ii-on-b-cell-defects-induced-by-invariant-chain-cd74-n-terminal-fragments
#12
Janna Schneppenheim, Ann-Christine Loock, Susann Hüttl, Michaela Schweizer, Renate Lüllmann-Rauch, Hans-Heinrich Oberg, Philipp Arnold, Christian H K Lehmann, Diana Dudziak, Dieter Kabelitz, Ralph Lucius, Ana-Maria Lennon-Duménil, Paul Saftig, Bernd Schröder
The invariant chain (CD74) mediates assembly and targeting of MHC class II (MHCII) complexes. In endosomes, CD74 undergoes sequential degradation by different proteases, including cathepsin S (CatS) and the intramembrane protease signal peptide peptidase-like 2a (SPPL2a). In their absence, CD74 N-terminal fragments (NTFs) accumulate. In SPPL2a(-/-) B cells, such an NTF impairs endosomal trafficking and BCR signal transduction. In mice, this leads to a loss of splenic B cells beyond the transitional stage 1...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28537552/structure-analyses-reveal-a-regulated-oligomerization-mechanism-of-the-plexind1-gipc-myosin-vi-complex
#13
Guijun Shang, Chad A Brautigam, Rui Chen, Defen Lu, Jesús Torres-Vázquez, Xuewu Zhang
The GIPC family adaptor proteins mediate endocytosis by tethering cargo proteins to the myosin VI motor. The structural mechanisms for the GIPC/cargo and GIPC/myosin VI interactions remained unclear. PlexinD1, a transmembrane receptor that regulates neuronal and cardiovascular development, is a cargo of GIPCs. GIPC-mediated endocytic trafficking regulates PlexinD1 signaling. Here, we unravel the mechanisms of the interactions among PlexinD1, GIPCs and myosin VI by a series of crystal structures of these proteins in apo or bound states...
May 24, 2017: ELife
https://www.readbyqxmd.com/read/28513921/chitin-induced-and-chitin-elicitor-receptor-kinase1-cerk1-phosphorylation-dependent-endocytosis-of-arabidopsis-thaliana-lysin-motif-containing-receptor-like-kinase5-lyk5
#14
Jan Erwig, Hassan Ghareeb, Michaela Kopischke, Ronja Hacke, Alexandra Matei, Elena Petutschnig, Volker Lipka
To detect potential pathogens, plants perceive the fungal polysaccharide chitin through receptor complexes containing lysin motif receptor-like kinases (LysM-RLKs). To investigate the ligand-induced spatial dynamics of chitin receptor components, we studied the subcellular behaviour of two Arabidopsis thaliana LysM-RLKs involved in chitin signalling, CHITIN ELICITOR RECEPTOR KINASE1 (CERK1) and LYSIN MOTIF-CONTAINING RECEPTOR-LIKE KINASE5. We performed standard and quantitative confocal laser scanning microscopy on stably transformed A...
May 17, 2017: New Phytologist
https://www.readbyqxmd.com/read/28507272/phosphatidylinositol-5-phosphate-4-kinase-regulates-early-endosomal-dynamics-during-clathrin-mediated-endocytosis
#15
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
#16
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/28500977/endocytosis-and-intracellular-traffic-of-cholesterol-pdmaema-liposome-complexes-in-human-epithelial-like-cells
#17
F Szymanowski, A A Hugo, P Alves, P N Simões, A Gómez-Zavaglia, Pablo F Pérez
Liposomes are generally used as delivery systems, as they are capable of encapsulating a wide variety of molecules (i.e. plasmids, recombinant proteins, therapeutic drugs). However, liposomal drug delivery have to fulfill different requirements, such as the effective internalization by the target cells and avoidance of the degradative activity of the intracellular compartments. The use of polymer lipid complexes (PLCs), by including different polymers in the liposome formulation, could improve internalization and intracellular release of drugs...
May 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28493289/intestinal-epithelial-claudins-expression-and-regulation-in-homeostasis-and-inflammation
#18
REVIEW
Vicky Garcia-Hernandez, Miguel Quiros, Asma Nusrat
The intestinal epithelium forms a highly dynamic and selective barrier that controls absorption of fluid and solutes while restricting pathogen access to underlying tissues. Barrier properties are achieved by intercellular junctions that include an apical tight junction (TJ) and subjacent adherens junctions and desmosomes. The TJ tetraspan claudin proteins form pores between epithelial cells to control paracellular fluid and ion movement. In addition to regulation of barrier function, claudin family members control epithelial homeostasis and are expressed in a spatiotemporal manner in the intestinal crypt-luminal axis...
June 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28481347/membrane-curvature-regulates-ligand-specific-membrane-sorting-of-gpcrs-in-living-cells
#19
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...
July 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28468881/mutations-in-the-transmembrane-domain-and-cytoplasmic-tail-of-hendra-virus-fusion-protein-disrupt-virus-like-particle-assembly
#20
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
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