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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/28298619/rab8-endocytosis-at-dynamic-cell-protrusions
#2
(no author information available yet)
No abstract text is available yet for this article.
March 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28228250/stratum-a-homolog-of-the-human-gef-mss4-partnered-with-rab8-controls-the-basal-restriction-of-basement-membrane-proteins-in-epithelial-cells
#3
Olivier Devergne, Gina H Sun, Trudi Schüpbach
The basement membrane (BM), a sheet of extracellular matrix lining the basal side of epithelia, is essential for epithelial cell function and integrity, yet the mechanisms that control the basal restriction of BM proteins are poorly understood. In epithelial cells, a specialized pathway is dedicated to restrict the deposition of BM proteins basally. Here, we report the identification of a factor in this pathway, a homolog of the mammalian guanine nucleotide exchange factor (GEF) Mss4, which we have named Stratum...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28225130/systematic-investigation-on-the-intracellular-trafficking-network-of-polymeric-nanoparticles
#4
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/28185347/salmonella-effector-sopd2-interferes-with-rab34-function
#5
Wei Xuan Teo, Zhe Yang, Markus Charles Kerr, Lin Luo, Zhong Guo, Kirill Alexandrov, Jenny Lea Stow, Rohan David Teasdale
Many intracellular pathogens have evolved highly specialized mechanisms to isolate themselves from the host cell's innate immune response while still obtaining the necessary nutrients to survive. Salmonella utilizes type 3 secretion systems (T3SSs) to deliver bacterial proteins called effectors, across the encompassing Salmonella Containing vacuole (SCV) membrane, to subvert the host's membrane trafficking pathways and alter other cellular processes. The Salmonella Pathogenicity Island (SPI)-2 effector SopD2 has recently been demonstrated to modulate multiple members of the Rab GTPase family such as Rab7, Rab8, Rab10, and Rab32 (D'Costa et al...
February 9, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28137756/endocytic-turnover-of-rab8-controls-cell-polarization
#6
Maite Vidal-Quadras, Mikkel R Holst, Monika K Francis, Elin Larsson, Mariam Hachimi, Wai Lok Yau, Johan Peränen, Fernando Martín-Belmonte, Richard Lundmark
Adaptation of cell shape and polarization through the formation and retraction of cellular protrusions requires balancing of endo- and exocytosis combined with fine-tuning of the local activity of small GTPases like Rab8. Here, we show that endocytic turnover of the plasma membrane at protrusions is directly coupled to surface removal and inactivation of Rab8. Removal is induced by reduced membrane tension and mediated by the GTPase regulator associated with focal adhesion kinase-1 (GRAF1), a regulator of clathrin independent endocytosis...
January 30, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28130450/rab8a-recruited-pi3k%C3%AE-regulates-signaling-and-cytokine-outputs-from-endosomal-toll-like-receptors
#7
Adam A Wall, Lin Luo, Yu Hung, Samuel J Tong, Nicholas D Condon, Antje Blumenthal, Matthew J Sweet, Jennifer L Stow
Lipopolysaccharide (LPS)-mediated activation of Toll-like receptor 4 (TLR4) in macrophages results in the coordinated release of proinflammatory cytokines, followed by regulatory mediators, to ensure that this potentially destructive pathway is tightly regulated. We previously showed that Rab8a recruits PI3Kγ for Akt-dependent signaling during TLR4 activation to limit the production of the pro-inflammatory cytokines IL-6 and IL-12p40, while enhancing the release of the regulatory/anti-inflammatory cytokine IL-10...
January 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28123016/cdk5-regulation-of-the-grab-mediated-rab8-rab11-cascade-in-axon-outgrowth
#8
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/27940993/cdk5-regulation-of-the-grab-mediated-rab8-rab11-cascade-in-axon-outgrowth
#9
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...
December 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27849131/spatial-rho-regulation-molecular-mechanisms-controlling-the-gap-protein-dlc3
#10
Janina Hendrick, Monilola A Olayioye
The spatial regulation of cellular Rho signaling by GEF and GAP proteins and the molecular mechanisms controlling the Rho regulators themselves are still incompletely understood. We previously reported that the poorly characterized RhoGAP protein DLC3 localizes to cell-cell adhesions and Rab8-positive membrane tubules. However, it was unclear how DLC3 is targeted to these subcellular sites to execute its functions. In our recent work, protein partners of DLC3 were identified by mass spectrometry, identifying the basolateral polarity protein Scribble as a scaffold for DLC3 at cell-cell contacts...
November 16, 2016: Small GTPases
https://www.readbyqxmd.com/read/27806291/role-for-the-ift-a-complex-in-selective-transport-to-the-primary-cilium
#11
Wenxiang Fu, Lei Wang, Sehyun Kim, Ji Li, Brian David Dynlacht
Intraflagellar transport sub-complex A (IFT-A) is known to regulate retrograde IFT in the cilium. To rigorously assess its other possible roles, we knocked out an IFT-A subunit, IFT121/WDR35, in mammalian cells and screened the localization of more than 50 proteins. We found that Wdr35 regulates cilium assembly by selectively regulating transport of distinct cargoes. Beyond its role in retrograde transport, we show that Wdr35 functions in fusion of Rab8 vesicles at the nascent cilium, protein exit from the cilium, and centriolar satellite organization...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27798239/phosphatidylinositol-4-kinase-ii%C3%AE-negatively-regulates-invadopodia-formation-and-suppresses-an-invasive-cellular-phenotype
#12
Ganiyu Olabanji Alli-Balogun, Christina A Gewinner, Ruth Jacobs, Janos Kriston-Vizi, Mark G Waugh, Shane Minogue
The type II phosphatidylinositol 4-kinase (PI4KII) enzymes synthesize the lipid phosphatidylinositol 4-phosphate (PI(4)P), which has been detected at the Golgi complex and endosomal compartments and recruits clathrin adaptors. Despite common mechanistic similarities between the isoforms, the extent of their redundancy is unclear. We found that depletion of PI4KIIα and PI4KIIβ using small interfering RNA led to actin remodeling. Depletion of PI4KIIβ also induced the formation of invadopodia containing membrane type I matrix metalloproteinase (MT1-MMP)...
December 15, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27767179/the-serologically-defined-colon-cancer-antigen-3-sdccag3-is-involved-in-the-regulation-of-ciliogenesis
#13
Fangyan Yu, Shruti Sharma, Agnieszka Skowronek, Kai Sven Erdmann
A primary cilium is present on most eukaryotic cells and represents a specialized organelle dedicated to signal transduction and mechanosensing. Defects in cilia function are the cause for several human diseases called ciliopathies. The serologically defined colon cancer antigen-3 (SDCCAG3) is a recently described novel endosomal protein mainly localized at early and recycling endosomes and interacting with several components of membrane trafficking pathways. Here we describe localization of SDCCAG3 to the basal body of primary cilia...
October 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27698943/intracellular-trafficking-network-of-protein-nanocapsules-endocytosis-exocytosis-and-autophagy
#14
Jinxie Zhang, Xudong Zhang, Gan Liu, Danfeng Chang, Xin Liang, Xianbing Zhu, Wei Tao, Lin Mei
The inner membrane vesicle system is a complex transport system that includes endocytosis, exocytosis and autophagy. However, the details of the intracellular trafficking pathway of nanoparticles in cells have been poorly investigated. Here, we investigate in detail the intracellular trafficking pathway of protein nanocapsules using more than 30 Rab proteins as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy. We observed that FITC-labeled protein nanoparticles were internalized by the cells mainly through Arf6-dependent endocytosis and Rab34-mediated micropinocytosis...
2016: Theranostics
https://www.readbyqxmd.com/read/27633000/a-ternary-complex-comprising-transportin1-rab8-and-the-ciliary-targeting-signal-directs-proteins-to-ciliary-membranes
#15
Viswanadh Madugula, Lei Lu
The sensory functions of cilia are dependent on the enrichment of cilium-resident proteins. Although it is known that ciliary targeting signals (CTSs) specifically target ciliary proteins to cilia, it is still unclear how CTSs facilitate the entry and retention of cilium-resident proteins at the molecular level. We found that non-ciliary membrane reporters can passively diffuse into cilia through the lateral transport pathway, and the translocation of membrane reporters through the ciliary diffusion barrier is facilitated by importin binding motifs and domains...
October 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27552051/bmerb-domains-are-bivalent-rab8-family-effectors-evolved-by-gene-duplication
#16
Amrita Rai, Anastasia Oprisko, Jeremy Campos, Yangxue Fu, Timon Friese, Aymelt Itzen, Roger S Goody, Emerich Mihai Gazdag, Matthias P Müller
In their active GTP-bound form, Rab proteins interact with proteins termed effector molecules. In this study, we have thoroughly characterized a Rab effector domain that is present in proteins of the Mical and EHBP families, both known to act in endosomal trafficking. Within our study, we show that these effectors display a preference for Rab8 family proteins (Rab8, 10, 13 and 15) and that some of the effector domains can bind two Rab proteins via separate binding sites. Structural analysis allowed us to explain the specificity towards Rab8 family members and the presence of two similar Rab binding sites that must have evolved via gene duplication...
August 23, 2016: ELife
https://www.readbyqxmd.com/read/27550519/arhgef10-directs-the-localization-of-rab8-to-rab6-positive-executive-vesicles
#17
Satoshi Shibata, Tsubasa Kawanai, Takayuki Hara, Asuka Yamamoto, Taro Chaya, Yasunori Tokuhara, Chinami Tsuji, Manabu Sakai, Taro Tachibana, Shinobu Inagaki
The function of ARHGEF10, a known guanine nucleotide exchange factor (GEF) for RhoA with proposed roles in various diseases, is poorly understood. To understand the precise function of this protein, we raised a monoclonal antibody against ARHGEF10 and determined its localization in HeLa cells. ARHGEF10 was found to localize to vesicles containing Rab6 (of which there are three isoforms, Rab6a, Rab6b and Rab6c), Rab8 (of which there are two isoforms, Rab8a and Rab8b), and/or the secretion marker neuropeptide Y (NPY)-Venus in a Rab6-dependent manner...
October 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27528616/bar-domain-containing-fam92-proteins-interact-with-chibby1-to-facilitate-ciliogenesis
#18
Feng-Qian Li, Xingwang Chen, Cody Fisher, Saul S Siller, Klara Zelikman, Ryoko Kuriyama, Ken-Ichi Takemaru
Chibby1 (Cby1) is a small, conserved coiled-coil protein that localizes to centrioles/basal bodies and plays a crucial role in the formation and function of cilia. During early stages of ciliogenesis, Cby1 is required for the efficient recruitment of small vesicles at the distal end of centrioles to facilitate basal body docking to the plasma membrane. Here, we identified family with sequence similarity 92, member A (FAM92A) and FAM92B, which harbor predicted lipid-binding BAR domains, as novel Cby1-interacting partners using tandem affinity purification and mass spectrometry...
November 1, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27494456/c9orf72-is-a-gdp-gtp-exchange-factor-for-rab8-and-rab39-and-regulates-autophagy
#19
Camille Corbier, Chantal Sellier
Amyotrophic Lateral Sclerosis and Frontotemporal Dementia (ALS-FTD) are devastating neurodegenerative disease affecting motoneurons from the spinal chord and neurons from the frontal and temporal cortex, respectively. The most common genetic cause for ALS-FTD is an expansion of GGGGCC repeats within the first intron of the C9ORF72 gene. However, little is known on the function of C9ORF72. Recently, other and we found that C9ORF72 forms a stable complex with the SMCR8 and WDR41 proteins. This complex acts as a GDP/GTP exchange factor for the small RAB GTPases Rab8a and Rab39b...
August 5, 2016: Small GTPases
https://www.readbyqxmd.com/read/27307040/vitamin-e-and-phosphoinositides-regulate-the-intracellular-localization-of-the-hepatic-%C3%AE-tocopherol-transfer-protein
#20
Stacey Chung, Mikel Ghelfi, Jeffrey Atkinson, Robert Parker, Jinghui Qian, Cathleen Carlin, Danny Manor
α-Tocopherol (vitamin E) is an essential nutrient for all vertebrates. From the eight naturally occurring members of the vitamin E family, α-tocopherol is the most biologically active species and is selectively retained in tissues. The hepatic α-tocopherol transfer protein (TTP) preferentially selects dietary α-tocopherol and facilitates its transport through the hepatocyte and its secretion to the circulation. In doing so, TTP regulates body-wide levels of α-tocopherol. The mechanisms by which TTP facilitates α-tocopherol trafficking in hepatocytes are poorly understood...
August 12, 2016: Journal of Biological Chemistry
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