Vesicular trafficking

Yen-Cheng Chen, Chetan Sood, Ashwanth C Francis, Gregory B Melikian, Robert M Dickson
Live cell fluorescence imaging is the method of choice for studying dynamic processes, such as nuclear transport, vesicular trafficking, and virus entry and egress. However, endogenous cellular autofluorescence masks useful fluorescence signal, limiting the ability to reliably visualize low-abundance fluorescent proteins. Here, we employed synchronously amplified fluorescence image recovery (SAFIRe), which optically alters ground versus photophysical dark state populations within fluorescent proteins to modulate and selectively detect their background-free emission...
November 6, 2019: Journal of Biological Chemistry
Farhath Sultana, Leslie R Morse, Gabriela Picotto, Weimin Liu, Prakash K Jha, Paul R Odgren, Ricardo A Battaglino
Bone resorption and organelle homeostasis in osteoclasts require specialized intracellular trafficking. Sorting nexin 10 (Snx10) is a member of the sorting nexin family of proteins that plays crucial roles in cargo sorting in the endosomal pathway by its binding to phosphoinositide(3)phosphate (PI3P) localized in early endosomes. We and others have shown previously that the gene encoding sorting Snx10 is required for osteoclast morphogenesis and function, as osteoclasts from humans and mice lacking functional Snx10 are dysfunctional...
November 6, 2019: Journal of Cellular Biochemistry
Yang Bai, Ying-Biao Chen, Xin-Tong Qiu, Yan-Bing Chen, Li-Tian Ma, Ying-Qi Li, Hong-Ke Sun, Ming-Ming Zhang, Ting Zhang, Tao Chen, Bo-Yuan Fan, Hui Li, Yun-Qing Li
BACKGROUND: Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis (CP). We hypothesized that the nucleus tractus solitarius (NTS), a primary central site that integrates pancreatic afferents apart from the thoracic spinal dorsal horn, plays a key role in the pathogenesis of visceral hypersensitivity in a rat model of CP. AIM: To investigate the role of the NTS in the visceral hypersensitivity induced by chronic pancreatitis...
October 28, 2019: World Journal of Gastroenterology: WJG
Elizabeth J Akin, Grant P Higerd, Malgorzata A Mis, Brian S Tanaka, Talia Adi, Shujun Liu, Fadia B Dib-Hajj, Stephen G Waxman, Sulayman D Dib-Hajj
Sodium channel NaV 1.7 controls firing of nociceptors, and its role in human pain has been validated by genetic and functional studies. However, little is known about NaV 1.7 trafficking or membrane distribution along sensory axons, which can be a meter or more in length. We show here with single-molecule resolution the first live visualization of NaV 1.7 channels in dorsal root ganglia neurons, including long-distance microtubule-dependent vesicular transport in Rab6A-containing vesicles. We demonstrate nanoclusters that contain a median of 12...
October 2019: Science Advances
Daniela Auer, Sophie Dorothea Hügelschäffer, Annette Barbara Fischer, Thomas Rudel
Chlamydia trachomatis is the main cause of sexually transmitted diseases worldwide. As obligate intracellular bacteria Chlamydia replicate in a membrane bound vacuole called inclusion and acquire nutrients for growth and replication from their host cells. However, like all intracellular bacteria, Chlamydia have to prevent eradication by the host's cell autonomous system. The chlamydial deubiquitinase Cdu1 is secreted into the inclusion membrane, facing the host cell cytosol where it deubiquitinates cellular proteins...
November 1, 2019: Cellular Microbiology
Alice Fletcher, Martin L Read, Caitlin E M Thornton, Dean P Larner, Vikki L Poole, Katie Brookes, Hannah R Nieto, Mohammed Alshahrani, Rebecca J Thompson, Gareth G Lavery, Iñigo Landa, James A Fagin, Moray J Campbell, Kristien Boelaert, Andrew S Turnell, Vicki E Smith, Christopher J McCabe
The sodium iodide symporter (NIS) is required for iodide uptake which facilitates thyroid hormone biosynthesis. NIS has been exploited for over 75 years in ablative radioiodine (RAI) treatment of thyroid cancer where its ability to transport radioisotopes depends on its localization to the plasma membrane. The advent of NIS-based in vivo imaging and theranostic strategies in other malignancies and disease modalities has recently increased the clinical importance of NIS. However, NIS trafficking remains ill-defined...
October 31, 2019: Cancer Research
Stefanie L Makowski, Ramya S Kuna, Seth J Field
The Golgi apparatus serves a key role in processing and sorting lipids and proteins for delivery to their final cellular destinations. Vesicle exit from the Golgi initiates with directional deformation of the lipid bilayer to produce a bulge. Several mechanisms have been described by which lipids and proteins can induce directional membrane curvature to promote vesicle budding. Here we review some of the mechanisms implicated in inducing membrane curvature at the Golgi to promote vesicular trafficking to various cellular destinations...
October 16, 2019: Advances in Biological Regulation
Giuseppina Grieco, Tongsong Wang, Ophélie Delcorte, Catherine Spourquet, Virginie Janssens, Aurélie Strickaert, Héloïse Gaide Chevronnay, Xiao-Hui Liao, Benoit Bilanges, Samuel Refetoff, Bart Vanhaesebroeck, Carine Maenhaut, Pierre J Courtoy, Christophe Etienne Pierreux
BACKGROUND: The production of thyroid hormones (T3, T4) depends on the organization of the thyroid in follicles, which are lined by a monolayer of thyrocytes with strict apico-basal polarity. This polarization supports vectorial transport of thyroglobulin for storage into, and recapture from, the colloid. It also allows selective addressing of channels, transporters, ion pumps and enzymes to their appropriate basolateral (NIS, SLC26A7 and Na+/K+-ATPase) or apical membrane domain (Anoctamin, SLC26A4, DUOX2, DUOXA2 and TPO)...
October 25, 2019: Thyroid: Official Journal of the American Thyroid Association
Jernej Jorgačevski, Alexei Verkhratsky
In the present issue of Acta Physiologica the team of researchers lead by Robert Zorec and Milos Pekny [1] examined the role of nesting (the intermediate filament associated with proliferation and stem cell capacity) in the regulation of vesicular trafficking in reactive astrocytes in vitro. Reactive astrogliosis is a complex of biochemical, morphological and functional metamorphoses of astrocytes in response to pathological insults to the brain and to the spinal cord. Instigation of astrogliosis by various pathology-related factors (generalised as damage-associated and pathogen-associated molecular patterns, DAMPs and PAMPs) produces multiple reactive phenotypes specific for the disease and context [2,3]...
October 23, 2019: Acta Physiologica
Wen-Hui Wang, Hong-Yan Li, Chao Qu, Ye-Jun Zhang, Wei Zou
Aberrant oxidative metabolism in cells is one of the hallmarks of cancer. Overproduction of reactive species promotes carcinogenesis by inducing genetic mutations and activating oncogenic pathways, and thus, antioxidant therapy is considered as an important strategy for cancer prevention and treatment. Caveolin-1 (Cav-1), a constituent protein of caveolae, is involved in not only the formation of the caveolae, vesicular transport, maintaining cholesterol homeostasis directly, but also many cellular physiological and pathological processes including growth, regulation of mitochondrial antioxidant level, apoptosis and carcinomas by interacting with a lot of signaling molecules through caveolin scaffolding domain...
October 25, 2019: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Julia M Laufer, Mark A Hauser, Ilona Kindinger, Vladimir Purvanov, Andreas Pauli, Daniel F Legler
Chemokine-guided cell migration is pivotal for many immunological and developmental processes. How chemokine receptor signaling persists to guarantee sustained directional migration despite receptor desensitization and internalization remains poorly understood. Here, we uncover a function for an intracellular pool of the chemokine receptor CCR7 present in human dendritic cells and cellular model systems. We find that CCR7 signaling, initiated at the plasma membrane, is translocated by joint trafficking of β-arrestin and Src kinase to endomembrane-residing CCR7...
October 22, 2019: Cell Reports
Johannes R Schmidt, Karina Geurtzen, Martin von Bergen, Kristin Schubert, Franziska Knopf
Long-term glucocorticoid administration in patients undergoing immunosuppressive and anti-inflammatory treatment is accompanied by impaired bone formation and increased fracture risk. Furthermore, glucocorticoid treatment can lead to impaired wound healing and altered cell metabolism. Recently, we showed that exposure of zebrafish to the glucocorticoid prednisolone during fin regeneration impacts negatively on the length, bone formation, and osteoblast function of the regenerate. The underlying cellular and molecular mechanisms of impairment, however, remain incompletely understood...
2019: Frontiers in Endocrinology
Wenjie Huang, Zhe Liu, Fan Yang, Huan Zhou, Xin Yong, Xiaoyu Yang, Yifei Zhou, Lijia Xue, Yihong Zhang, Dingdong Liu, Wentong Meng, Wenming Zhang, Xiaohu Zhang, Xiaofei Shen, Qingxiang Sun, Li Li, Cong Ma, Yuquan Wei, Daniel D Billadeau, Xianming Mo, Da Jia
Pontocerebellar hypoplasia (PCH) is a group of neurological disorders that affect the development of the brain, in particular, the pons and cerebellum. Homozygous mutations of TBC1D23 have been found recently to lead to PCH; however, the underlying molecular mechanisms remain unclear. Here, we show that the crystal structure of the TBC1D23 C-terminal domain adopts a Pleckstrin homology domain fold and selectively binds to phosphoinositides, in particular, PtdIns(4)P, through one surface while binding FAM21 via the opposite surface...
October 17, 2019: Proceedings of the National Academy of Sciences of the United States of America
Vanessa M D'Costa, Etienne Coyaud, Kirsten C Boddy, Estelle M N Laurent, Jonathan St-Germain, Taoyingnan Li, Sergio Grinstein, Brian Raught, John H Brumell
Many bacterial pathogens express virulence proteins that are translocated into host cells (herein referred to as effectors), where they can interact with target proteins to manipulate host cell processes. These effector-host protein interactions are often dynamic and transient in nature, making them difficult to identify using traditional interaction-based methods. Here, we performed a systematic comparison between proximity-dependent biotin labelling (BioID) and immunoprecipitation coupled with mass spectrometry to investigate a series of Salmonella type 3 secreted effectors that manipulate host intracellular trafficking (SifA, PipB2, SseF, SseG and SopD2)...
October 14, 2019: Nature Microbiology
Natalia H Revelo, Martin Ter Beest, Geert van den Bogaart
Immune-cell activation by inflammatory stimuli triggers the transcription and translation of large amounts of cytokines. The transport of newly synthesized cytokines to the plasma membrane by vesicular trafficking can be rate-limiting for the production of these cytokines, and immune cells upregulate their exocytic machinery concomitantly with increased cytokine expression in order to cope with the increasing demand for trafficking. Whereas it is logical that trafficking is rate-limiting for regulated secretion where an intracellular pool of molecules is waiting to be released, the reason for this is not obvious for constitutively secreted cytokines, such as interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α)...
October 10, 2019: Journal of Cell Science
Abigail Buchwalter, Roberta Schulte, Hsiao Tsai, Juliana Capitanio, Martin Hetzer
The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM's unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ ...
October 10, 2019: ELife
Shailaja Seetharaman, Sandrine Etienne-Manneville
Cell adhesion to the extracellular matrix is essential for cellular processes, such as migration and invasion. In response to cues from the microenvironment, integrin-mediated adhesions alter cellular behaviour through cytoskeletal rearrangements. The tight association of the actin cytoskeleton with adhesive structures has been extensively studied, whereas the microtubule network in this context has gathered far less attention. In recent years, however, microtubules have emerged as key regulators of cell adhesion and migration through their participation in adhesion turnover and cellular signalling...
October 9, 2019: Journal of Cell Science
Kyle L Morris, Joseph R Jones, Mary Halebian, Shenping Wu, Michael Baker, Jean-Paul Armache, Amaurys Avila Ibarra, Richard B Sessions, Alexander D Cameron, Yifan Cheng, Corinne J Smith
Clathrin forms diverse lattice and cage structures that change size and shape rapidly in response to the needs of eukaryotic cells during clathrin-mediated endocytosis and intracellular trafficking. We present the cryo-EM structure and molecular model of assembled porcine clathrin, providing insights into interactions that stabilize key elements of the clathrin lattice, namely, between adjacent heavy chains, at the light chain-heavy chain interface and within the trimerization domain. Furthermore, we report cryo-EM maps for five different clathrin cage architectures...
October 2019: Nature Structural & Molecular Biology
Boris Simonetti, Blessy Paul, Karina Chaudhari, Saroja Weeratunga, Florian Steinberg, Madhavi Gorla, Kate J Heesom, Greg J Bashaw, Brett M Collins, Peter J Cullen
Protein trafficking requires coat complexes that couple recognition of sorting motifs in transmembrane cargoes with biogenesis of transport carriers. The mechanisms of cargo transport through the endosomal network are poorly understood. Here, we identify a sorting motif for endosomal recycling of cargoes, including the cation-independent mannose-6-phosphate receptor and semaphorin 4C, by the membrane tubulating BAR domain-containing sorting nexins SNX5 and SNX6. Crystal structures establish that this motif folds into a β-hairpin, which binds a site in the SNX5/SNX6 phox homology domains...
October 2019: Nature Cell Biology
Luis Sanchez-Pulido, Chris P Ponting
SUMMARY: CPLANE is a protein complex required for assembly and maintenance of primary cilia. It contains several proteins, such as INTU, FUZ, WDPCP, JBTS17, and RSG1 (REM2- and RAB-like small GTPase 1), whose genes are mutated in ciliopathies. Using two contrasting evolutionary analyses, coevolution-based contact prediction and sequence conservation, we first identified the INTU/FUZ heterodimer as a novel member of homologous HerMon (Hermansky-Pudlak syndrome and MON1-CCZ1) complexes...
September 28, 2019: Bioinformatics
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