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141.
A.V. Kuznetsov 《Computer methods in biomechanics and biomedical engineering》2013,16(6):711-722
This paper simulates an axon with a region of reversed microtubule (MT) polarity, and investigates how the degree of polar mismatching in this region affects the formation of organelle traps in the axon. The model is based on modified Smith–Simmons equations governing molecular-motor-assisted transport in neurons. It is established that the structure that develops as a result of a region with disoriented MTs consists of two organelle traps, the trap to the left of this region accumulates plus-end-oriented organelles and the trap to the right of this region accumulates minus-end-oriented organelles. The presence of such a structure is shown to inhibit the transport of organelles down the axon. The degree by which the transport of organelles is inhibited depends on the degree of polar mismatching of MTs in the region between MT traps. Four cases with a different degree of polar mismatching are investigated. 相似文献
142.
Elsa Seixas Mafalda Barros Miguel C. Seabra Duarte C. Barral 《Traffic (Copenhagen, Denmark)》2013,14(8):871-885
Rab and ADP‐ribosylation factor (Arf) family proteins are master regulators of membrane trafficking and are involved in all steps of vesicular transport. These families of small guanine‐nucleotide‐binding (G) proteins are well suited to regulate membrane trafficking processes since their nucleotide state determines their conformation and the capacity to bind to a multitude of effectors, which mediate their functions. In recent years, several inherited diseases have been associated with mutations in genes encoding proteins belonging to these two families or in proteins that regulate their GTP‐binding cycle. The genetic diseases that are caused by defects in Rabs, Arfs or their regulatory proteins are heterogeneous and display diverse symptoms. However, these diseases mainly affect two types of subcellular compartments, namely lysosome‐related organelles and cilia. Also, several of these diseases affect the nervous system. Thus, the study of these diseases represents an opportunity to understand their etiology and the molecular mechanisms involved, as well as to develop novel therapeutic strategies . 相似文献
143.
Grace H.E. Kim Roya M. Dayam Akriti Prashar Mauricio Terebiznik Roberto J. Botelho 《Traffic (Copenhagen, Denmark)》2014,15(10):1143-1163
Macrophages eliminate pathogens and cell debris through phagocytosis, a process by which particulate matter is engulfed and sequestered into a phagosome. Nascent phagosomes are innocuous organelles resembling the plasma membrane. However, through a maturation process, phagosomes are quickly remodeled by fusion with endosomes and lysosomes to form the phagolysosome. Phagolysosomes are highly acidic and degradative leading to particle decomposition. Phagosome maturation is intimately dependent on the endosomal pathway, during which diverse cargoes are sorted for recycling to the plasma membrane or for degradation in lysosomes. Not surprisingly, various regulators of the endosomal pathway are also required for phagosome maturation, including phosphatidylinositol‐3‐phosphate, an early endosomal regulator. However, phosphatidylinositol‐3‐phosphate can be modified by the lipid kinase PIKfyve into phosphatidylinositol‐3,5‐bisphosphate, which controls late endosome/lysosome functions. The role of phosphatidylinositol‐3,5‐bisphosphate in macrophages and phagosome maturation remains basically unexplored. Using Fcγ receptor‐mediated phagocytosis as a model, we describe our research showing that inhibition of PIKfyve hindered certain steps of phagosome maturation. In particular, PIKfyve antagonists delayed removal of phosphatidylinositol‐3‐phosphate and reduced acquisition of LAMP1 and cathepsin D, both common lysosomal proteins. Consistent with this, the degradative capacity of phagosomes was reduced but phagosomes appeared to still acidify. We also showed that trafficking to lysosomes and their degradative capacity was reduced by PIKfyve inhibition. Overall, we provide evidence that PIKfyve, likely through phosphatidylinositol‐3,5‐bisphosphate synthesis, plays a significant role in endolysosomal and phagosome maturation in macrophages. 相似文献
144.
145.
George Papageorgiou 《Science activities》2013,50(2):19-22
For most middle school-level students, summarizing main ideas can prove to be difficult, especially for those with low vocabulary and language acquisition skills. Working specifically with students who are English Language Learners (ELLs) and in a special education program, we discovered that teaching summarization as a reading strategy increased students' abilities to (a) acquire and use information and (b) better comprehend science concepts. In combination with other vocabulary attainment activities, summary frames enhanced the students' ability to apply information to discussions, laboratory reports, and projects. In this article, we demonstrate how to use the summary frame strategy in the context of a lesson on cells. This lesson allows for (a) knowledge of terminology through vocabulary card activities, (b) comprehension of concepts presented through summary frame activities, and (c) application of concepts through cell models and organelle classroom responsibilities. 相似文献
146.
Jürgen Fritsch Vladimir Tchikov Lena Hennig Ralph Lucius Stefan Schütze 《Traffic (Copenhagen, Denmark)》2019,20(3):246-258
Homeostasis and the complex functions of organisms and cells rely on the sophisticated spatial and temporal regulation of signaling in different intra‐ and extracellular compartments and via different mediators. We here present a set of fast and easy to use protocols for the target‐specific immunomagnetic enrichment of receptor containing endosomes (receptosomes), plasma membranes, lysosomes and exosomes. Isolation of subcellular organelles and exosomes is prerequisite for and will advance their detailed subsequent biochemical and functional analysis. Sequential application of the different subprotocols allows isolation of morphological and functional intact organelles from one pool of cells. The enrichment is based on a selective labelling using receptor ligands or antibodies together with superparamagnetic microbeads followed by separation in a patented matrix‐free high‐gradient magnetic purification device. This unique magnetic chamber is based on a focusing system outside of the empty separation column, generating an up to 3 T high‐gradient magnetic field focused at the wall of the column. 相似文献
147.
In cells at steady state, two forms of cell compartmentalization coexist: membrane‐bound organelles and phase‐separated membraneless organelles that are present in both the nucleus and the cytoplasm. Strikingly, cellular stress is a strong inducer of the reversible membraneless compartments referred to as stress assemblies. Stress assemblies play key roles in survival during cell stress and in thriving of cells upon stress relief. The two best studied stress assemblies are the RNA‐based processing‐bodies (P‐bodies) and stress granules that form in response to oxidative, endoplasmic reticulum (ER), osmotic and nutrient stress as well as many others. Interestingly, P‐bodies and stress granules are heterogeneous with respect to both the pathways that lead to their formation and their protein and RNA content. Furthermore, in yeast and Drosophila, nutrient stress also leads to the formation of many other types of prosurvival cytoplasmic stress assemblies, such as metabolic enzymes foci, proteasome storage granules, EIF2B bodies, U‐bodies and Sec bodies, some of which are not RNA‐based. Nutrient stress leads to a drop in cytoplasmic pH, which combined with posttranslational modifications of granule contents, induces phase separation. 相似文献
148.
Stephanie Spannl Maria Tereshchenko Giovanni J. Mastromarco Sean J. Ihn Hyun O. Lee 《Traffic (Copenhagen, Denmark)》2019,20(12):890-911
The intracellular environment is partitioned into functionally distinct compartments containing specific sets of molecules and reactions. Biomolecular condensates, also referred to as membrane‐less organelles, are diverse and abundant cellular compartments that lack membranous enclosures. Molecules assemble into condensates by phase separation; multivalent weak interactions drive molecules to separate from their surroundings and concentrate in discrete locations. Biomolecular condensates exist in all eukaryotes and in some prokaryotes, and participate in various essential house‐keeping, stress‐response and cell type‐specific processes. An increasing number of recent studies link abnormal condensate formation, composition and material properties to a number of disease states. In this review, we discuss current knowledge and models describing the regulation of condensates and how they become dysregulated in neurodegeneration and cancer. Further research on the regulation of biomolecular phase separation will help us to better understand their role in cell physiology and disease. 相似文献
149.
Changes in the concentration of cytosolic Ca2+ form the basis of a ubiquitous signal transduction pathway. Accumulating evidence implicates acidic organelles in the control of Ca2+ dynamics in organisms across phyla. In this special issue, we discuss Ca2+ signalling by these “acidic Ca2+ stores” which include acidocalcisomes, vacuoles, the endo-lysosomal system, lysosome-related organelles, secretory vesicles and the Golgi complex. Ca2+ release from these morphologically very different organelles is mediated by members of the TRP channel superfamily and two-pore channels. Inositol trisphosphate and ryanodine receptors which are traditionally viewed as endoplasmic reticulum Ca2+ release channels can also mobilize acidic Ca2+ stores. Ca2+ uptake into acidic Ca2+ stores is driven by Ca2+ ATPases and Ca2+/H+ exchangers. In animal cells, the Ca2+-mobilizing messenger NAADP plays a central role in mediating Ca2+ signals from acidic Ca2+ stores through activation of two-pore channels. These signals are important for several physiological processes including muscle contraction and differentiation. Dysfunctional acidic Ca2+ stores have been implicated in diseases such as acute pancreatitis and lysosomal storage disorders. Acidic Ca2+ stores are therefore emerging as essential components of the Ca2+ signalling network and merit extensive further study. 相似文献
150.
Sophie J. Deharvengt Dan Tse Olga Sideleva Caitlin McGarry Jason R. Gunn Daniel S. Longnecker Catherine Carriere Radu V. Stan 《Journal of cellular and molecular medicine》2012,16(11):2690-2700
PV1 is an endothelial‐specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour‐bearing mice by single‐dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down‐regulation by shRNAs inhibits the growth of established tumours derived from two different human pancreatic adenocarcinoma cell lines (AsPC‐1 and BxPC‐3). The effect observed is because of down‐regulation of PV1 in the tumour endothelial cells of host origin, PV1 being specifically expressed in tumour vascular endothelial cells and not in cancer or other stromal cells. There are no differences in vascular density of tumours treated or not with PV1 shRNA, and gain and loss of function of PV1 in endothelial cells does not modify either their proliferation or migration, suggesting that tumour angiogenesis is not impaired. Together, our data argue that down‐regulation of PV1 in tumour endothelial cells results in the inhibition of tumour growth via a mechanism different from inhibiting angiogenesis. 相似文献