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Vesicular trafficking

George M Carman, Gil-Soo Han
Phosphatidic acid (PA) phosphatase is an evolutionarily conserved enzyme that plays a major role in lipid homeostasis by controlling the cellular levels of its substrate, PA, and its product, diacylglycerol. These lipids are essential intermediates for the synthesis of triacylglycerol and membrane phospholipids; they also function in lipid signaling, vesicular trafficking, lipid droplet formation, and phospholipid synthesis gene expression. The importance of PA phosphatase to lipid homeostasis and cell physiology is exemplified in yeast, mice, and humans by a host of cellular defects and lipid-based diseases associated with loss or overexpression of the enzyme activity...
December 7, 2018: Journal of Lipid Research
Domenico Roberti, Renata Conforti, Teresa Giugliano, Barbara Brogna, Immacolata Tartaglione, Maddalena Casale, Giulio Piluso, Silverio Perrotta
Diamond-Blackfan anemia (DBA) is a rare congenital erythroid aplasia with a highly heterogeneous genetic background; it usually occurs in infancy. Approximately 30-40% of patients have other associated congenital anomalies; in particular, facial anomalies, such as cleft palate, are part of about 10% of the DBA clinical presentations. Pierre Robin sequence (PRS) is a heterogeneous condition, defined by the presence of the triad of glossoptosis, micrognathia and cleft palate; it occurs in 1/8500 to 1/14,000 births...
2018: Frontiers in Genetics
Marta Portela, Berta Segura-Collar, Irene Argudo, Almudena Sáiz, Ricardo Gargini, Pilar Sánchez-Gómez, Sergio Casas-Tintó
Genetic lesions in glioblastoma (GB) include constitutive activation of PI3K and EGFR pathways to drive cellular proliferation and tumor malignancy. An RNAi genetic screen, performed in Drosophila melanogaster to discover new modulators of GB development, identified a member of the secretory pathway: kish/TMEM167A. Downregulation of kish/TMEM167A impaired fly and human glioma formation and growth, with no effect on normal glia. Glioma cells increased the number of recycling endosomes, and reduced the number of lysosomes...
December 2, 2018: Glia
Maria Daniela Garcia-Castillo, Wayne I Lencer, Daniel J-F Chinnapen
Absorption and secretion of peptide and protein cargoes across single-cell thick mucosal and endothelial barriers occurs by active endocytic and vesicular trafficking that connects one side of the epithelial or endothelial cell (the lumen) with the other (the serosa or blood). Assays that assess this pathway must robustly control for non-specific and passive solute flux through weak or damaged intercellular junctions that seal the epithelial or endothelial cells together. Here we describe an in vitro cell culture Transwell assay for transcytosis of therapeutic peptides linked covalently to various species of the glycosphingolipid GM1...
October 20, 2018: Bio-protocol
Elizabeth Michele Davies, Rajendra Gurung, Kai Qin Le, Christina Anne Mitchell
Phosphoinositide signaling regulates numerous downstream effectors that mediate cellular processes which influence cell cycle progression, migration, proliferation, growth, survival, metabolism and vesicular trafficking. A prominent role for phosphoinositide 3-kinase, which generates phosphatidylinositol 3,4,5-trisphosphate, a phospholipid that activates a plethora of effectors including AKT and FOXO during embryonic and postnatal angiogenesis, has been described. In addition, phosphatidylinositol 3-phosphate signaling is required for endosomal trafficking, which contributes to vascular remodeling...
November 26, 2018: Advances in Biological Regulation
Ezra Aksoy, Loredana Saveanu, Bénédicte Manoury
Phosphoinositide-3 kinases (PI3Ks) generate 3-phosphorylated phosphoinositide lipids that are implicated in many biological processes in homeostatic states and pathologies such as cancer, inflammation and autoimmunity. Eight isoforms of PI3K exist in mammals and among them the class I PI3K, p110γ, and PI3Kδ, and class III Vps34 being the most expressed and well characterized in immune cells. Following engagement of pathogen recognition receptors (PRRs), PI3Ks coordinate vital cellular processes of signaling and vesicular trafficking in innate phagocytes such as macrophages and professional antigen presenting dendritic cells (DCs)...
2018: Frontiers in Immunology
Jingjing Cheng, Qingqing Lu, Li Song, Margaret S Ho
Protein aggregation and accumulation are common pathological hallmarks in neurodegenerative diseases. To efficiently clear and eliminate such aggregation becomes an important cellular strategy for cell survival. Lewy bodies inclusion and aggregation of α-Synuclein (α-Syn) during the pathogenesis of Parkinson's disease (PD) serve as a good example and are potentially linked to other pathological PD features such as progressive dopaminergic neuron cell death, behavioral defects, and nonmotor symptoms like anosmia, cognitive impairment, and depression...
January 2018: ASN Neuro
Javad Alizadeh, Shahla Shojaei, Simone da Silva Rosa, Adel Rezaei Moghadam, Amir A Zeki, Mohammad Hashemi, Marek J Los, Joseph W Gordon, Saeid Ghavami
The Rho GTPase family belongs to the Ras superfamily and includes approximately 20 members in humans. Rho GTPases are important in the regulation of diverse cellular functions, including cytoskeletal dynamics, cell motility, cell polarity, axonal guidance, vesicular trafficking, and cell cycle control. Changes in Rho GTPase signaling play an essential regulatory role in many pathological conditions, such as cancer, central nervous system diseases, and immune system-dependent diseases. The posttranslational modification of Rho GTPases (i...
November 11, 2018: Journal of Visualized Experiments: JoVE
Alejandrina Hernández-López, Mauricio Díaz, Jonathan Rodríguez-López, Gabriel Guillén, Federico Sánchez, Claudia Díaz-Camino
Bax-inhibitor 1 (BI-1) is a cell death suppressor conserved in all eukaryotes that modulates cell death in response to abiotic stress and pathogen attack in plants. Thus far nothing is known about its role in the establishment of symbiotic interactions. Here, we demonstrate the functional relevance of an Arabidopsisthaliana BI-1 homolog (PvBI-1a) to symbiosis between the common bean (Phaseolus vulgaris) and Rhizobium tropici. We show that the PvBI-1a expression changes observed during early symbiosis resemble those of some defence-response related proteins...
November 21, 2018: Journal of Experimental Botany
María Pilar Madrigal Verdú, Adrián Portalés, María Pérez SanJuan, Sandra Jurado
Soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins mediate membrane fusion events in eukaryotic cells. Traditionally recognized as major players in regulating presynaptic neurotransmitter release, accumulative evidence over recent years has identified several SNARE proteins implicated in important postsynaptic processes such as neurotransmitter receptor trafficking and synaptic plasticity. Here we analyze the emerging data revealing this novel functional dimension for SNAREs with a focus on the molecular specialization of vesicular recycling and fusion in dendrites compared to those at axon terminals and its impact in synaptic transmission and plasticity...
November 17, 2018: Neuroscience
Chaithanya Kotyada, Mintu Chandra, Aashutosh Tripathi, Anil R Narooka, Sunando Datta, Akash Verma
Entamoeba histolytica, the causative agent of amoebic dysentery, liver abscess and colitis, exploits its vesicular trafficking machinery for survival and virulence. Rab family of small GTPases play a key role in the vesicular transport by undergoing the GTP/GDP cycle which is central to the biological processes. Amoebic genome encodes several atypical Rab GTPases which are unique due to absence of conserved sequence motif(s) or atypical residues in their catalytic site [Saito-Nakano et al., 2005 ]. Previously, EhRab21 has been reported to involve in amoebic invasion and migration [Emmanuel et al...
November 30, 2018: Biochemical and Biophysical Research Communications
Lingling Zhao, Xin Ji, Xiangxiang Zhang, Lin Li, Yaping Jin, Wei Liu
The Birt-Hogg-Dubé (BHD) syndrome related protein FLCN has recently been implicated in the vesicular trafficking processes by interacting with several Rab family GTPases. In the previous studies, we have shown that FLCN could inhibit the binding of overexpressed PAT1, which is a membrane-bound amino acid transporter, to the lysosome in human embryonic kidney 293 cells. This tends to stabilize the lysosomal amino acid pool that is a critical signal to activate the mTORC1 signalling pathway. However, the mechanisms of FLCN during this process remain unexplored...
November 16, 2018: Journal of Cell Science
Jeffrey J Hodgson, Nicolas Buchon, Gary W Blissard
The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is a model enveloped DNA virus that infects and replicates in lepidopteran insect cells, and can efficiently enter a wide variety of non-host cells. Budded virions of AcMNPV enter cells by endocytosis and traffic to the nucleus where the virus initiates gene expression and genome replication. While trafficking of nucleocapsids by actin propulsion has been studied in detail, other important components of trafficking during entry remain poorly understood...
November 13, 2018: Virology
Antonio Pisano, Francesco Albano, Eleonora Vecchio, Maurizio Renna, Giuseppe Scala, Ileana Quinto, Giuseppe Fiume
Protein ubiquitylation plays a central role in eukaryotic cell physiology. It is involved in several regulatory processes, ranging from protein folding or degradation, subcellular localization of proteins, vesicular trafficking and endocytosis to DNA repair, cell cycle, innate immunity, autophagy, and apoptosis. As such, it is reasonable that pathogens have developed a way to exploit such a crucial system to enhance their virulence against the host. Hence, bacteria have evolved a wide range of effectors capable of mimicking the main players of the eukaryotic ubiquitin system, in particular ubiquitin ligases, by interfering with host physiology...
November 13, 2018: International Journal of Molecular Sciences
Yaming Jiu
Both the cytoskeletal intermediate filaments (IFs) and cytoplasmic caveolae contribute to active processes such as cell migration, morphogenesis and vesicular trafficking, but the interplay between these two systems has remained elusive. Here, we find that vimentin and nestin IFs interact with caveolae central component caveolin-1 (CAV-1) and importantly, restrain the intracellular trafficking of CAV-1 positive vesicles by serving as a physical barrier. Consequently, CAV-1 vesicles show less density and mobility in vimentin IFs enriched region, which is a substrate stiffness independent process...
December 9, 2018: Biochemical and Biophysical Research Communications
Catalina Martínez Jaramillo, Claudia M Trujillo-Vargas
Bi-allelic mutations in LRBA (from Lipopolysaccharide-responsive and beige-like anchor protein ) result in a primary immunodeficiency with clinical features ranging from hypogammaglobulinemia and lymphoproliferative syndrome to inflammatory bowel disease and heterogeneous autoimmune manifestations. LRBA deficiency has been shown to affect vesicular trafficking, autophagy and apoptosis, which may lead to alterations of several molecules and processes that play key roles for immunity. In this review, we will discuss the relationship of LRBA with the endovesicular system in the context of receptor trafficking, autophagy and apoptosis...
September 30, 2018: Colombia Médica: CM
Juhyung Lee, Yihong Ye
Protein secretion in general depends on signal sequence (also named leader sequence), a hydrophobic segment located at or close to the NH2-terminus of a secretory or membrane protein. This sequence guides the entry of nascent polypeptides into the lumen or membranes of the endoplasmic reticulum (ER) for folding, assembly, and export. However, evidence accumulated in recent years has suggested the existence of a collection of unconventional protein secretion (UPS) mechanisms that are independent of the canonical vesicular trafficking route between the ER and the plasma membrane (PM)...
November 3, 2018: Cells
Youn-Sang Jung, Sohee Jun, Moon Jong Kim, Sung Ho Lee, Han Na Suh, Esther M Lien, Hae-Yun Jung, Sunhye Lee, Jie Zhang, Jung-In Yang, Hong Ji, Ji Yuan Wu, Wenqi Wang, Rachel K Miller, Junjie Chen, Pierre D McCrea, Scott Kopetz, Jae-Il Park
Vesicular acidification and trafficking are associated with various cellular processes. However, their pathologic relevance to cancer remains elusive. We identified transmembrane protein 9 (TMEM9) as a vesicular acidification regulator. TMEM9 is highly upregulated in colorectal cancer. Proteomic and biochemical analyses show that TMEM9 binds to and facilitates assembly of vacuolar-ATPase (v-ATPase), a vacuolar proton pump, resulting in enhanced vesicular acidification and trafficking. TMEM9-v-ATPase hyperactivates Wnt/β-catenin signalling via lysosomal degradation of adenomatous polyposis coli (APC)...
December 2018: Nature Cell Biology
Liangcheng Jiao, Qinghua Zhou, Zhixin Su, Yunjun Yan
This study is dedicated to efficiently produce Rhizopus oryzae lipase (ROL) by optimizing the expression of multiple expression-related helper proteins in Pichia pastoris . A series of engineered strains harboring different copy numbers of the ROL gene and different copies of the chaperone Pdi gene were first constructed to examine the influence of Pdi gene copy number on ROL production. The results showed that multiple copies of Pdi gene did not significantly improve ROL expression. Then, the effect of the co-overexpression of 10 expression-related helper proteins on ROL secretion was investigated by screening 20 colonies of each transformants...
October 28, 2018: International Journal of Molecular Sciences
Mohammed H Mosa, Ophélie Nicolle, Sophia Maschalidi, Fernando E Sepulveda, Aurelien Bidaud-Meynard, Constantin Menche, Birgitta E Michels, Grégoire Michaux, Geneviève de Saint Basile, Henner F Farin
Background & Aims: Microvillus inclusion disease (MVID) is a congenital intestinal malabsorption disorder caused by defective apical vesicular transport. Existing cellular models do not fully recapitulate this heterogeneous pathology. The aim of this study was to characterize 3-dimensional intestinal organoids that continuously generate polarized absorptive cells as an accessible and relevant model to investigate MVID. Methods: Intestinal organoids from Munc18-2 / Stxbp2 -null mice that are deficient for apical vesicular transport were subjected to enterocyte-specific differentiation protocols...
2018: Cellular and Molecular Gastroenterology and Hepatology
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