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https://www.readbyqxmd.com/read/28213463/membrane-transport-across-polarized-epithelia
#1
Maria Daniela Garcia-Castillo, Daniel J-F Chinnapen, Wayne I Lencer
Polarized epithelial cells line diverse surfaces throughout the body forming selective barriers between the external environment and the internal milieu. To cross these epithelial barriers, large solutes and other cargoes must undergo transcytosis, an endocytic pathway unique to polarized cell types, and significant for the development of cell polarity, uptake of viral and bacterial pathogens, transepithelial signaling, and immunoglobulin transport. Here, we review recent advances in our knowledge of the transcytotic pathway for proteins and lipids...
February 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28208320/dynamic-model-for-kinesin-mediated-long-range-transport-and-its-local-traffic-jam-caused-by-tau-proteins
#2
Woochul Nam, Bogdan I Epureanu
In neurons, several intracellular cargoes are transported by motor proteins (kinesins) which walk on microtubules (MTs). However, kinesins can possibly unbind from the MTs before they reach their destinations. The unbound kinesins randomly diffuse in neurons until they bind to MTs. Then, they walk again along the MTs to continue their tasks. Kinesins repeat this cycle of motion until they transport their cargoes to the destinations. However, most previous models mainly focused on the motion of kinesins when they walk on MTs...
January 2017: Physical Review. E
https://www.readbyqxmd.com/read/28202504/expression-profiling-of-circulating-microvesicles-reveals-intercellular-transmission-of-oncogenic-pathways
#3
Gloria Milani, Tobia Lana, Silvia Bresolin, Sanja Aveic, Anna Pasto, Chiara Frasson, Geertruy Te Kronnie
: Circulating microvesicles (MVs) have been described as important players in cell-to-cell communication carrying biological information under normal or pathological condition. MVs released by cancer cells may incorporate diverse biomolecules (e.g. active lipids, proteins and RNA) which can be delivered and internalized by recipient cells, potentially altering gene expression of recipient cells and eventually impacting disease progression. Leukemia in vitro model systems were used to investigate MVs as vehicles of protein-coding messages...
February 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28198592/bone-marrow-derived-mesenchymal-stem-cells-derived-exosomes-promote-survival-of-retinal-ganglion-cells-through-mirna-dependent-mechanisms
#4
Ben Mead, Stanislav Tomarev
The loss of retinal ganglion cells (RGC) and their axons is one of the leading causes of blindness and includes traumatic (optic neuropathy) and degenerative (glaucoma) eye diseases. Although no clinical therapies are in use, mesenchymal stem cells (MSC) have demonstrated significant neuroprotective and axogenic effects on RGC in both of the aforementioned models. Recent evidence has shown that MSC secrete exosomes, membrane enclosed vesicles (30-100 nm) containing proteins, mRNA and miRNA which can be delivered to nearby cells...
February 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28198180/engineering-recombinant-virus-like-nanoparticles-from-plants-for-cellular-delivery
#5
Lou Brillault, Philippe V Jutras, Noor Dashti, Eva C Thuenemann, Garry Morgan, George P Lomonossoff, Michael J Landsberg, Frank Sainsbury
Understanding capsid assembly following recombinant expression of viral structural proteins is critical to the design and modification of virus-like nanoparticles for biomedical and nanotechnology applications. Here, we use plant-based transient expression of the Bluetongue virus (BTV) structural proteins, VP3 and VP7, to obtain high yields of empty and green fluorescent protein (GFP)-encapsidating core-like particles (CLPs) from leaves. Single-particle cryo-electron microscopy of both types of particles revealed considerable differences in CLP structure compared to the crystal structure of infection-derived CLPs; in contrast, the two recombinant CLPs have an identical external structure...
February 15, 2017: ACS Nano
https://www.readbyqxmd.com/read/28197909/sumo-and-nucleocytoplasmic-transport
#6
Christopher Ptak, Richard W Wozniak
The transport of proteins between the nucleus and cytoplasm occurs through nuclear pore complexes and is facilitated by numerous transport factors. These transport processes are often regulated by post-translational modification or, reciprocally, transport can function to control post-translational modifications through regulated transport of key modifying enzymes. This interplay extends to relationships between nucleocytoplasmic transport and SUMO-dependent pathways. Examples of protein sumoylation inhibiting or stimulating nucleocytoplasmic transport have been documented, both through its effects on the physical properties of cargo molecules and by directly regulating the functions of components of the nuclear transport machinery...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28193860/investigations-of-human-myosin-vi-targeting-using-optogenetically-controlled-cargo-loading
#7
Alexander R French, Tobin R Sosnick, Ronald S Rock
Myosins play countless critical roles in the cell, each requiring it to be activated at a specific location and time. To control myosin VI with this specificity, we created an optogenetic tool for activating myosin VI by fusing the light-sensitive Avena sativa phototropin1 LOV2 domain to a peptide from Dab2 (LOVDab), a myosin VI cargo protein. Our approach harnesses the native targeting and activation mechanism of myosin VI, allowing direct inferences on myosin VI function. LOVDab robustly recruits human full-length myosin VI to various organelles in vivo and hinders peroxisome motion in a light-controllable manner...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193700/the-nuclear-transport-receptor-importin-11-is-a-tumor-suppressor-that-maintains-pten-protein
#8
Muhan Chen, Dawid G Nowak, Navneet Narula, Brian Robinson, Kaitlin Watrud, Alexandra Ambrico, Tali M Herzka, Martha E Zeeman, Matthias Minderer, Wu Zheng, Saya H Ebbesen, Kendra S Plafker, Carlos Stahlhut, Victoria M Y Wang, Lorna Wills, Abu Nasar, Mireia Castillo-Martin, Carlos Cordon-Cardo, John E Wilkinson, Scott Powers, Raffaella Sordella, Nasser K Altorki, Vivek Mittal, Brendon M Stiles, Scott M Plafker, Lloyd C Trotman
Phosphatase and tensin homologue (PTEN) protein levels are critical for tumor suppression. However, the search for a recurrent cancer-associated gene alteration that causes PTEN degradation has remained futile. In this study, we show that Importin-11 (Ipo11) is a transport receptor for PTEN that is required to physically separate PTEN from elements of the PTEN degradation machinery. Mechanistically, we find that the E2 ubiquitin-conjugating enzyme and IPO11 cargo, UBE2E1, are limiting factors for PTEN degradation...
February 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28192660/in-vivo-imaging-of-the-stability-and-sustained-cargo-release-of-an-injectable-amphipathic-peptide-based-hydrogel
#9
Edith Oyen, Charlotte Martin, Vicky Caveliers, Annemieke Madder, Bruno Van Mele, Richard Hoogenboom, Sophie Hernot, Steven Ballet
Hydrogels are promising materials for biomedical applications such as tissue engineering and controlled drug release. In the past two decades, the peptide hydrogel subclass has attracted an increasing level of interest from the scientific community because of its numerous advantages, such as biocompatibility, biodegradability, and, most importantly, injectability. Here, we report on a hydrogel consisting of the amphipathic hexapeptide H-FEFQFK-NH2, which has previously shown promising in vivo properties in terms of releasing morphine...
February 20, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28191928/self-assembling-multidomain-peptide-nanofibers-for-delivery-of-bioactive-molecules-and-tissue-regeneration
#10
Amanda N Moore, Jeffrey D Hartgerink
Multidomain peptides (MDPs) are a class of self-assembling peptides that are organized in a β-sheet motif, resulting in a nanofibrous architecture. This structure is stabilized by hydrophobic packing in the fiber core and a hydrogen-bonding network down the fiber long axis. Under easily controllable conditions, regulated by electrostatic interactions between the peptides and the pH and salt composition of the solvent, the nanofiber length can be dramatically extended, resulting in fiber entanglement and hydrogel formation...
February 13, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28190655/development-of-helix-stabilized-cell-penetrating-peptides-containing-cationic-%C3%AE-%C3%AE-disubstituted-amino-acids-as-helical-promoters
#11
Hiroko Yamashita, Takashi Misawa, Makoto Oba, Masakazu Tanaka, Mikihiko Naito, Masaaki Kurihara, Yosuke Demizu
Cell-penetrating peptides (CPP) have attracted many scientists' attention as intracellular delivery tools due to their high cargo molecule transportation efficiency and low cytotoxicity. Therefore, in many research fields CPP, such as HIV-Tat and oligoarginine (Rn), are used to deliver hydrophilic drugs and biomolecules, including proteins, DNA, and RNA. We designed four types of CPP that contained cationic α,α-disubstituted amino acids (Api(C2Gu) and Api(C4Gu)) as helical promoters; i.e., 1-4 [FAM-β-Ala-(l-Arg-l-Arg-Xaa)3-(Gly)3-NH2 (1: Xaa=Api(C2Gu), 2: Xaa=Api(C4Gu)), 3: FAM-β-Ala-(l-Arg)8-Api(C2Gu)-(Gly)3-NH2, and 4: FAM-β-Ala-(l-Arg)5-Api(C2Gu)-(l-Arg)2-Api(C2Gu)-(Gly)3-NH2], and investigated their preferred secondary structures and cell membrane-penetrating ability...
February 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28186701/bone-marrow-derived-mesenchymal-stem-cells-derived-exosomes-promote-survival-of-retinal-ganglion-cells-through-mirna-dependent-mechanisms
#12
Ben Mead, Stanislav Tomarev
The loss of retinal ganglion cells (RGC) and their axons is one of the leading causes of blindness and includes traumatic (optic neuropathy) and degenerative (glaucoma) eye diseases. Although no clinical therapies are in use, mesenchymal stem cells (MSC) have demonstrated significant neuroprotective and axogenic effects on RGC in both of the aforementioned models. Recent evidence has shown that MSC secrete exosomes, membrane enclosed vesicles (30-100 nm) containing proteins, mRNA and miRNA which can be delivered to nearby cells...
January 26, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28185357/yeast-dynamin-interaction-with-escrt-proteins-at-the-endosome
#13
Bryan T Banh, Hyoeun McDermott, Sara Woodman, Shiva Kumar Goud Gadila, Uma Saimani, John Cw Short, Kyoungtae Kim
The dynamin-like protein, Vps1, is a GTPase involved in cargo sorting and membrane remodeling in multiple cellular trafficking pathways. Recently, Vps1 has been shown to genetically interact with ESCRT subunits. We tested the hypothesis that the functional connection of Vps1 with some of these subunits of ESCRT complexes occurs via a physical interaction. By utilizing the yeast two-hybrid system, we revealed that Vps1 physically interacts with the ESCRT-II subunits, Vps22 and Vps36, and the ESCRT-III subunit Vps24...
February 9, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28184302/the-role-of-exosomes-in-the-pathogenesis-of-alzheimer-disease
#14
REVIEW
Tingting Xiao, Weiwei Zhang, Bin Jiao, Chu-Zheng Pan, Xixi Liu, Lu Shen
Exosomes are small vesicles secreted by most cell types including neurons that function in intercellular communication through transfer of their cargo or encapsulate and eliminate unnecessary cellular components and therefore have a broad impact on nerve development, activation and regeneration. In addition, exosomes have been observed to be involved in spreading pathological misfolded proteins, thereby leading to the onset and propagation of disease. Alzheimer disease (AD) is the most common form of dementia and characterized by two types of lesions: amyloid plaques and neurofibrillary tangles...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28182119/biodegradable-mesoporous-delivery-system-for-biomineralization-precursors
#15
Hong-Ye Yang, Li-Na Niu, Jin-Long Sun, Xue-Qing Huang, Dan-Dan Pei, Cui Huang, Franklin R Tay
Scaffold supplements such as nanoparticles, components of the extracellular matrix, or growth factors have been incorporated in conventional scaffold materials to produce smart scaffolds for tissue engineering of damaged hard tissues. Due to increasing concerns on the clinical side effects of using large doses of recombinant bone-morphogenetic protein-2 in bone surgery, it is desirable to develop an alternative nanoscale scaffold supplement that is not only osteoinductive, but is also multifunctional in that it can perform other significant bone regenerative roles apart from stimulation of osteogenic differentiation...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28179530/japanese-encephalitis-virus-ns5-inhibits-the-type-i-interferon-production-by-blocking-the-nuclear-translocation-of-irf3-and-nf-%C3%AE%C2%BAb
#16
Jing Ye, Zheng Chen, Yunchuan Li, Zikai Zhao, Wen He, Ali Zohaib, Yunfeng Song, Chenglin Deng, Bo Zhang, Huanchun Chen, Shengbo Cao
The type I interferon (IFN) response is part of a first-line defense against viral infection. To initiate replication, viruses have developed powerful evasion strategies to counteract host IFN responses. In present study, we found that Japanese encephalitis virus (JEV) NS5 protein could inhibit double strand RNA (dsRNA)-induced IFN-β expression in a dose-dependent manner. Our data further demonstrated that JEV NS5 suppressed the activation of IFN transcriptional factors, IRF3 and NF-κB. However, there was no defect in the phosphorylation of IRF3 and degradation of IκB, an upstream inhibitor of NF-κB, upon NS5 expression, indicating a direct inhibition of the nuclear localization of IRF3 and NF-κB by NS5...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28179529/differential-disruption-of-nucleocytoplasmic-trafficking-pathways-by-rhinovirus-2a-proteases
#17
Kelly Watters, Bahar Inankur, Jaye C Gardiner, Jay Warrick, Nathan M Sherer, John Yin, Ann C Palmenberg
The RNA rhinoviruses (RV) encode 2A proteases (2A(pro)) that contribute essential polyprotein processing and host-cell shutoff functions during infection, including the cleavage of Phe/Gly-containing nucleoporin proteins (Nups) within nuclear pore complexes (NPC). Within the 3 RV species, multiple divergent genotypes encode diverse 2A(pro) sequences which act differentially on specific Nups. Since only subsets of Phe/Gly motifs, particularly those within Nup62, Nup98 and Nup153, are recognized by transport receptors (karyopherins) when trafficking large molecular cargos through the NPC, the processing preferences of individual 2A(pro) predict RV genotype-specific targeting of NPC pathways and cargos...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28177202/biofluid-triggered-burst-release-from-an-adaptive-covalently-assembled-dipeptide-nanocontainer-for-emergency-treatment
#18
Jinbo Fei, He Zhang, Anhe Wang, Chenchen Qin, Huimin Xue, Junbai Li
The construction of quickly dissociating containers holding bioactive components that meet the extreme requirements of emergency treatment is highly desirable but remains a great challenge. Here the use of small-molecule-induced dynamic covalent assembly is reported for simple and tunable fabrication of a biocompatible diphenylalanine-based nanocontainer toward rapidly responsive cargo delivery. The assembled nanocontainer can adaptively encapsulate various charged or neutral molecules. Upon biofluid trigger, the encapsulated molecules and bioactive proteins are released in a burst (within 5 s) from the nanocontainer due to highly sensitive deprotonation-mediated disruption of hydrogen bonding...
February 8, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28169082/autophagy-receptors-and-neurodegenerative-diseases
#19
REVIEW
Zhiqiang Deng, Kerry Purtell, Veronik Lachance, Mitchell S Wold, Shi Chen, Zhenyu Yue
Previously thought of as a nonselective digestion process, autophagy is now known to specifically degrade aggregated proteins and damaged cellular organelles through the action of autophagy receptors, which provides cellular quality control and maintains homeostasis. Autophagy receptors recognize and recruit specific cargoes to the autophagosome-lysosome pathway for degradation in ubiquitin-dependent and -independent manners, and their functions (in selective autophagy) are regulated by protein modifications, for example, phosphorylation and ubiquitination...
February 3, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28166455/structural-and-mechanistic-insights-into-nuclear-transport-and-delivery-of-the-critical-pluripotency-factor-oct4-to-dna
#20
Takahide Okuyama, Ryosuke Yamagishi, Jiro Shimada, Masaaki Ikeda, Yayoi Maruoka, Hiroki Kaneko
Oct4 is a master regulator of the induction and maintenance of cellular pluripotency, and has crucial roles in early stages of differentiation. It is the only factor that cannot be substituted by other members of the same protein family to induce pluripotency. However, although Oct4 nuclear transport and delivery to target DNA are critical events for reprogramming to pluripotency, little is known about the molecular mechanism. Oct4 is imported to the nucleus by the classical nuclear transport mechanism, which requires importin α as an adaptor to bind the nuclear localization signal (NLS)...
February 6, 2017: Journal of Biomolecular Structure & Dynamics
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