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https://www.readbyqxmd.com/read/28334871/proteomics-insights-into-infantile-neuronal-ceroid-lipofuscinosis-cln1-point-to-the-involvement-of-cilia-pathology-in-the-disease
#1
Michal Segal-Salto, Karin Hansson, Tamar Sapir, Anna Kaplan, Talia Levy, Michaela Schwizer, Michael Frotscher, Peter James, Orly Reiner
Mutations in the depalmitoylation enzyme, palmitoyl protein thioesterase (PPT1), result in the early onset neurodegenerative disease known as Infantile Neuronal Ceroid Lipofuscinosis. Here, we provide proteomic evidence suggesting that PPT1 deficiency could be considered as a ciliopathy. Analysis of membrane proteins from brain enriched for acylated proteins from neonate Ppt1 knock out and control mice revealed a list of 88 proteins with differential expression levels. Amongst them, we identified Rab3IP, which regulates ciliogenesis in concert with Rab8 and Rab11...
March 6, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28303263/astrocyte-ca-2-influx-negatively-regulates-neuronal-activity
#2
Yao V Zhang, Kiel G Ormerod, J Troy Littleton
Maintenance of neural circuit activity requires appropriate regulation of excitatory and inhibitory synaptic transmission. Recently, glia have emerged as key partners in the modulation of neuronal excitability; however, the mechanisms by which glia regulate neuronal signaling are still being elucidated. Here, we describe an analysis of how Ca(2+) signals within Drosophila astrocyte-like glia regulate excitability in the nervous system. We find that Drosophila astrocytes exhibit robust Ca(2+) oscillatory activity manifested by fast, recurrent microdomain Ca(2+) fluctuations within processes that infiltrate the synaptic neuropil...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28294115/phosphorylation-of-rab-coupling-protein-by-lmtk3-controls-rab14-dependent-epha2-trafficking-to-promote-cell-cell-repulsion
#3
Christine Gundry, Sergi Marco, Elena Rainero, Bryan Miller, Emmanuel Dornier, Louise Mitchell, Patrick T Caswell, Andrew D Campbell, Anna Hogeweg, Owen J Sansom, Jennifer P Morton, Jim C Norman
The Rab GTPase effector, Rab-coupling protein (RCP) is known to promote invasive behaviour in vitro by controlling integrin and receptor tyrosine kinase (RTK) trafficking, but how RCP influences metastasis in vivo is unclear. Here we identify an RTK of the Eph family, EphA2, to be a cargo of an RCP-regulated endocytic pathway which controls cell:cell repulsion and metastasis in vivo. Phosphorylation of RCP at Ser(435) by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser(897) by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart...
March 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28251922/early-stages-of-functional-diversification-in-the-rab-gtpase-gene-family-revealed-by-genomic-and-localization-studies-in-paramecium-species
#4
Lydia J Bright, Jean-Francois Gout, Michael Lynch
New gene functions arise within existing gene families as a result of gene duplication and subsequent diversification. To gain insight into the steps that lead to the functional diversification of paralogs, we tracked duplicate retention patterns, expression-level divergence, and subcellular markers of functional diversification in the Rab GTPase gene family in three Paramecium aurelia species. Following whole genome duplication, Rab GTPase duplicates are more highly retained than other genes in the genome, but appear to be diverging more rapidly in expression levels, consistent with early steps in functional diversification...
March 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28235896/pathogenic-huntington-alters-bmp-signaling-and-synaptic-growth-through-local-disruptions-of-endosomal-compartments
#5
Yulia Akbergenova, J Troy Littleton
Huntington's disease (HD) is a neurodegenerative disorder caused by expansion of a polyglutamine (polyQ) stretch within the Huntingtin (Htt) protein. Pathogenic Htt disrupts multiple neuronal processes, including gene expression, axonal trafficking, proteasome and mitochondrial activity, and intracellular vesicle trafficking. However, the primary pathogenic mechanism and subcellular site of action for mutant Htt are still unclear. Using a Drosophila HD model, we found that pathogenic Htt expression leads to a profound overgrowth of synaptic connections that directly correlates with the levels of Htt at nerve terminals...
February 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28235866/rab11-fip3-regulation-of-lck-endosomal-traffic-controls-tcr-signal-transduction
#6
Jérôme Bouchet, Iratxe Del Río-Iñiguez, Elena Vázquez-Chávez, Rémi Lasserre, Sonia Agüera-González, Céline Cuche, Mary W McCaffrey, Vincenzo Di Bartolo, Andrés Alcover
The role of endosomes in receptor signal transduction is a long-standing question, which remains largely unanswered. The T cell Ag receptor and various components of its proximal signaling machinery are associated with distinct endosomal compartments, but how endosomal traffic affects T cell signaling remains ill-defined. In this article, we demonstrate in human T cells that the subcellular localization and function of the protein tyrosine kinase Lck depends on the Rab11 effector FIP3 (Rab11 family interacting protein-3)...
February 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28228550/interaction-of-phosphorylated-rab11-fip2-with-eps15-regulates-apical-junction-composition
#7
Lynne A Lapierre, Elizabeth H Manning, Kenya M Mitchell, Cathy M Caldwell, James R Goldenring
MARK2 regulates the establishment of polarity in MDCK cells in part through phosphorylation of serine 227 of Rab11-FIP2. We have now identified Eps15 as an interacting partner of phospho-S227-Rab11-FIP2 (pS227-FIP2). During recovery from low calcium, Eps15 localized to the lateral membrane, prior to pS227-FIP2 arrival. Later in recovery, Eps15 and pS227-FIP2 co-localized at the lateral membrane. In MDCK cells expressing the pseudophosphorylated FIP2 mutant, FIP2(S227E), during recovery from low calcium, Eps15 was trapped and never localized to the lateral membrane...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28225130/systematic-investigation-on-the-intracellular-trafficking-network-of-polymeric-nanoparticles
#8
Jinxie Zhang, Danfeng Chang, Yao Yang, Xudong Zhang, Wei Tao, Lijuan Jiang, Xin Liang, Hsiangi Tsai, Laiqiang Huang, Lin Mei
Polymeric nanoparticles such as PLGA-based nanoparticles are emerging as promising carriers for controlled drug delivery. However, little is known about the intracellular trafficking network of polymeric nanoparticles. Here, more than 30 Rab proteins were used as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy to investigate in detail the intracellular trafficking pathways of PLGA nanoparticles. We observed that coumarin-6-loaded PLGA nanoparticles were internalized by the cells mainly through caveolin and clathrin-dependent endocytosis and Rab34-mediated macropinocytosis...
February 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28209731/transport-of-fungal-rab11-secretory-vesicles-involves-myosin-5-dynein-dynactin-p25-and-kinesin-1-and-is-independent-of-kinesin-3
#9
Miguel A Peñalva, Jun Zhang, Xin Xiang, Areti Pantazopoulou
Hyphal tip cells of the fungus Aspergillus nidulans are useful to study long-range intracellular traffic. Post-Golgi secretory vesicles (SVs) containing the RAB11 orthologue RabE engage myosin-5 as well as plus-end- and minus-end-directed microtubule motors, providing an experimental system to investigate the interplay between microtubule and actin motors acting on the same cargo. By exploiting the fact that depolymerization of F-actin 'unleashes' SVs focused at the apex by myosin-5 to microtubule-dependent motors, we establish that the minus-end directed transport of SVs requires the dynein/dynactin supercomplex...
February 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28180992/comprehensive-functional-analysis-of-rab-gtpases-in-drosophila-nephrocytes
#10
Yulong Fu, Jun-Yi Zhu, Fujian Zhang, Adam Richman, Zhanzheng Zhao, Zhe Han
The Drosophila nephrocyte is a critical component of the fly renal system and bears structural and functional homology to podocytes and proximal tubule cells of the mammalian kidney. Investigations of nephrocyte cell biological processes are fundamental to understanding the insect renal system. Nephrocytes are highly active in endocytosis and vesicle trafficking. Rab GTPases regulate endocytosis and trafficking but specific functions of nephrocyte Rabs remain undefined. We analyzed Rab GTPase expression and function in Drosophila nephrocytes and found that 11 out of 27 Drosophila Rabs were required for normal activity...
February 8, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28143705/non-autonomous-role-of-cdc42-in-cell-cell-communication-during-collective-migration
#11
Nathalie Colombié, Valérie Choesmel-Cadamuro, Jennifer Series, Gregory Emery, Xiaobo Wang, Damien Ramel
Collective cell migration is involved in numerous processes both physiological, such as embryonic development, and pathological such as metastasis. Compared to single cell migration, collective motion requires cell behaviour coordination through an as-yet poorly understood but critical cell-cell communication mechanism. Using Drosophila border cell migration, we show here that the small Rho GTPase Cdc42 regulates cell-cell communication. Indeed, we demonstrate that Cdc42 controls protrusion formation in a cell non-autonomous manner...
March 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28123016/cdk5-regulation-of-the-grab-mediated-rab8-rab11-cascade-in-axon-outgrowth
#12
Kotaro Furusawa, Akiko Asada, Pamela Urrutia, Christian Gonzalez-Billault, Mitsunori Fukuda, Shin-Ichi Hisanaga
Neurons communicate with each other through their axons and dendrites. However, a full characterization of the molecular mechanisms involved in axon and dendrite formation is still incomplete. Neurite outgrowth requires the supply of membrane components for surface expansion. Two membrane sources for axon outgrowth are suggested: Golgi secretary vesicles and endocytic recycling endosomes. In non-neuronal cells, trafficking of secretary vesicles from Golgi is regulated by Rab8, a member of Rab small GTPases, and that of recycling endosomes is by Rab11, another member of Rabs...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100639/munc13-4-functions-as-a-ca2-sensor-for-homotypic-secretory-granule-fusion-to-generate-endosomal-exocytic-vacuoles
#13
Sang Su Woo, Declan J James, Thomas F J Martin
Munc13-4 is a Ca(2+)-dependent SNARE- and phospholipid-binding protein that localizes to and primes secretory granules (SGs) for Ca(2+)-evoked secretion in various secretory cells. Studies in mast cell-like RBL-2H3 cells provides direct evidence that Munc13-4 with its two Ca(2+)-binding C2 domains functions as a Ca(2+) sensor for SG exocytosis. Unexpectedly, Ca(2+) stimulation also generated large (>2.4 μm diameter) Munc13-4(+)/Rab7(+)/Rab11(+) endosomal vacuoles. Vacuole generation involved the homotypic fusion of Munc13-4(+)/Rab7(+) SGs followed by a merge with Rab11(+) endosomes, and depended on Ca(2+) binding to Munc13-4...
January 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28088841/intracellular-fate-of-ureaplasma-parvum-entrapped-by-host-cellular-autophagy
#14
Fumiko Nishiumi, Michinaga Ogawa, Yukiko Nakura, Yusuke Hamada, Masahiro Nakayama, Jiro Mitobe, Atsushi Hiraide, Norio Sakai, Makoto Takeuchi, Tamotsu Yoshimori, Itaru Yanagihara
Genital mycoplasmas, including Ureaplasma spp., are among the smallest human pathogenic bacteria and are associated with preterm birth. Electron microscopic observation of U. parvum showed that these prokaryotes have a regular, spherical shape with a mean diameter of 146 nm. U. parvum was internalized into HeLa cells by clathrin-mediated endocytosis and survived for at least 14 days around the perinuclear region. Intracellular U. parvum reached endosomes in HeLa cells labeled with EEA1, Rab7, and LAMP-1 within 1 to 3 hr...
January 15, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28057129/-effect-of-rab11-gene-expression-on-the-invasion-and-migration-of-cervical-cancer-cell-line-siha-in-hypoxia
#15
H Xu, Y Yuan, J Y Ji, Q Jiang, L J Niu, N L Liu, L Z Zhang, X Wang
Objective: To explore the expression of Ras-related protein 11 (Rab11) in hypoxia, the effect of Rab11 on the invasion and migration of cervical cancer cell line SiHa and its possible mechanism. Methods: SiHa cells were divided into 4 groups, the normoxic blank group (normal culture in normoxia), the hypoxic blank group (normal culture in hypoxia), the negative control group [transfection of negative control small interfering RNA (siRNA) in hypoxia], the Rab11-siRNA group (transfection of Rab11 siRNA in hypoxia)...
December 25, 2016: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/28035375/high-rab11-fip4-expression-predicts-poor-prognosis-and-exhibits-tumor-promotion-in-pancreatic-cancer
#16
Yun He, Mengsi Ye, Lingling Zhou, Yunfeng Shan, Guangrong Lu, Yuhui Zhou, Jinwei Zhong, Jihang Zheng, Zhanxiong Xue, Zhenzhai Cai
Some studies have demonstrated that Rab11-family interacting proteins (Rab11-FIPs) are connected with the tumorigenesis, and they may act as tumor promoters in some cancers. The clinicopathological significance of Rab11-family interacting protein 4 (Rab11-FIP4 ) expression and its possible effects on pancreatic cancer (PC) are still undiscovered. In this study, Rab11-FIP4 protein expression level in 60 PC specimens and pair-matched non-cancerous samples were detected by immunohistochemistry analysis. The results were analysed and compared with each patients' clinical data...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28017473/huntingtin-mediated-multipolar-bipolar-transition-of-newborn-cortical-neurons-is-critical-for-their-postnatal-neuronal-morphology
#17
Monia Barnat, Julien Le Friec, Caroline Benstaali, Sandrine Humbert
In the developing cortex, projection neurons undergo multipolar-bipolar transition, radial-directed migration, and maturation. The contribution of these developmental steps to the structure of the adult cortex is not completely understood. Here, we report that huntingtin (HTT), the protein mutated in Huntington's disease, is enriched in polarizing projection neurons. The depletion of HTT in postmitotic projection neurons leads to the mislocalization of layer-specific neuronal populations in the mouse neocortex...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28003861/rei-1-a-novel-rab11-gef-with-a-sh3bp5-domain
#18
Aisa Sakaguchi, Miyuki Sato, Ken Sato
The small GTPase Rab proteins are key regulators of membrane trafficking. Rab11 is one of the best-characterized molecules among the Rab family proteins and it plays multiple roles in endocytic recycling, exocytosis, and cytokinesis. However, it remains unclear how Rab11 is activated at a precise timing and location and regulates its diverse functions. Specifically, our knowledge of the upstream regulatory factors that activate Rab11 is limited. In this regard, we have identified the RAB-11-interacting protein-1 (REI-1) as a novel guanine nucleotide exchange factor (GEF) for RAB-11 in Caenorhabditis elegans (C...
2016: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/28003220/recycling-of-apolipoprotein-a-after-plgrkt-mediated-endocytosis-of-lipoprotein-a
#19
Monika Sharma, Gregory M Redpath, Michael J Williams, Sally P McCormick
RATIONALE: Lipoprotein(a) [Lp(a)] is a low density lipoprotein (LDL)-like lipoprotein and important cardiovascular risk factor whose cognate receptor and intracellular fate remains unknown. OBJECTIVE: Our study aimed to determine the intracellular trafficking pathway for Lp(a) and the receptor responsible for its uptake in liver cells. METHODS AND RESULTS: Human hepatoma (HepG2) cells were treated with Lp(a) purified from human plasma and Lp(a) uptake studied using western blot analysis and intracellular localisation of Lp(a) by confocal microscopy...
December 21, 2016: Circulation Research
https://www.readbyqxmd.com/read/27973418/varicella-zoster-virus-infectious-cycle-er-stress-autophagic-flux-and-amphisome-mediated-trafficking
#20
REVIEW
Charles Grose, Erin M Buckingham, John E Carpenter, Jeremy P Kunkel
Varicella-zoster virus (VZV) induces abundant autophagy. Of the nine human herpesviruses, the VZV genome is the smallest (~124 kbp), lacking any known inhibitors of autophagy, such as the herpes simplex virus ICP34.5 neurovirulence gene. Therefore, this review assesses the evidence for VZV-induced cellular stress, endoplasmic-reticulum-associated degradation (ERAD), and autophagic flux during the VZV infectious cycle. Even though VZV is difficult to propagate in cell culture, the biosynthesis of the both N- and O-linked viral glycoproteins was found to be abundant...
December 10, 2016: Pathogens
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