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Intracellular Locations (intracellular + locations)
Selected AbstractsTrafficking of neurokinin receptors: regulation, mechanism and functionEXPERIMENTAL DERMATOLOGY, Issue 9 2004N. Bunnett Cellular responses to agonists of G-protein-coupled receptors (GPCRs) depend in large part on the trafficking of receptors between the plasma membrane and intracellular locations. Receptor activation usually triggers rapid endocytosis of receptors, which either recycle to the cell surface or are targeted for degradation, depending on the receptor in question and the nature of the stimulation. Activation of neurokinin receptors (NKRs) induces membrane translocation of G-protein receptor kinases, which phosphorylate the receptors and ,-arrestins, which interact with phosphorylated receptors. ,-arrestins: 1) uncouple receptors from G-proteins to mediate desensitization; 2) are adaptors for clathrin and AP-2 and mediate clathrin and dynamin-dependent endocytosis of receptors; and 3) interact with components of the MAP kinase pathway such as src, and thereby determine the subcellular location and function of activated MAP kinases. The fate of endocytosed NKRs depends on the receptor and the nature of the stimulus. Transient stimulation with low concentrations of SP (1 nm, 10 min) induces rapid recycling of the NK1R from superficially located endosomes by a mechanism that is mediated by rab4a and rab11a. Higher concentrations of SP (10 nm) induce rab5a-dependent trafficking of the NK1R to perinuclear sorting endosomes and a gradual recycling to the plasma membrane. Continuous stimulation with high concentrations of SP (100 nm, 180 min) induces NK1R ubiquitination and trafficking for degradation. The fate of endocytosed receptors also depends on their interaction with ,-arrestins. The NK1R forms stable high-affinity interactions with both ,-arrestins 1 and 2 at the plasma membrane and in endosomes, whereas the NK3R interacts transiently only with ,-arrestin 2 at the cell surface. The nature of these interactions is specified by domains in the intracellular loop 3 and the carboxyl terminus and determine the rate of recycling and resensitization of these receptors. [source] Mouse cytosolic sulfotransferase SULT2B1b interacts with cytoskeletal proteins via a proline/serine-rich C-terminusFEBS JOURNAL, Issue 18 2010Katsuhisa Kurogi Cytosolic sulfotransferase (SULT) SULT2B1b had previously been characterized as a cholesterol sulfotransferase. Like human SULT2B1, mouse SULT2B1b contains a unique, 31 amino acid C-terminal sequence with a proline/serine-rich region, which is not found in members of other SULT families. To gain insight into the functional relevance of this proline/serine-rich region, we constructed a truncated mouse SULT2B1b lacking the 31 C-terminal amino acids, and compared it with the wild-type enzyme. Enzymatic characterization indicated that the catalytic activity was not significantly affected by the absence of those C-terminal residues. Glutathione S -transferase pulldown assays showed that several proteins interacted with mouse SULT2B1b specifically through this C-terminal proline/serine-rich region. Peptide mass fingerprinting revealed that of the five SULT2B1b-binding proteins analyzed, three were cytoskeletal proteins and two were cytoskeleton-binding molecular chaperones. Furthermore, wild-type mouse SULT2B1b, but not the truncated enzyme, was associated with the cytoskeleton in experiments with a cytoskeleton-stabilizing buffer. Collectively, these results suggested that the unique, extended proline/serine-rich C-terminus of mouse SULT2B1b is important for its interaction with cytoskeletal proteins. Such an interaction may allow the enzyme to move along microfilaments such as actin filaments, and catalyze the sulfation of hydroxysteroids, such as cholesterol and pregnenolone, at specific intracellular locations. Structured digital abstract ,,MINT-7975854: Sult2B1b (uniprotkb:O35400) physically interacts (MI:0914) with Myosin-Ic (uniprotkb:Q9WTI7), Alpha-actinin-1 (uniprotkb:Q7TPR4), Alpha-actinin-4 (uniprotkb:P57780), HSP 90-beta (uniprotkb:P11499), Hsc70, (uniprotkb:P63017), Beta-actin (uniprotkb:P60710) and Gamma-actin (uniprotkb:P63260) by pull down (MI:0096) [source] Heat stress activates phospholipase D and triggers PIP2 accumulation at the plasma membrane and nucleusTHE PLANT JOURNAL, Issue 1 2009Michael Mishkind Summary Heat stress induces an array of physiological adjustments that facilitate continued homeostasis and survival during periods of elevated temperatures. Here, we report that within minutes of a sudden temperature increase, plants deploy specific phospholipids to specific intracellular locations: phospholipase D (PLD) and a phosphatidylinositolphosphate kinase (PIPK) are activated, and phosphatidic acid (PA) and phosphatidylinositol 4,5-bisphosphate (PIP2) rapidly accumulate, with the heat-induced PIP2 localized to the plasma membrane, nuclear envelope, nucleolus and punctate cytoplasmic structures. Increases in the steady-state levels of PA and PIP2 occur within several minutes of temperature increases from ambient levels of 20,25°C to 35°C and above. Similar patterns were observed in heat-stressed Arabidopsis seedlings and rice leaves. The PA that accumulates in response to temperature increases results in large part from the activation of PLD rather than the sequential action of phospholipase C and diacylglycerol kinase, the alternative pathway used to produce this lipid. Pulse-labelling analysis revealed that the PIP2 response is due to the activation of a PIPK rather than inhibition of a lipase or a PIP2 phosphatase. Inhibitor experiments suggest that the PIP2 response requires signalling through a G-protein, as aluminium fluoride blocks heat-induced PIP2 increases. These results are discussed in the context of the diverse cellular roles played by PIP2 and PA, including regulation of ion channels and the cytoskeleton. [source] Intracellular replication of Salmonella typhimurium strains in specific subsets of splenic macrophages in vivoCELLULAR MICROBIOLOGY, Issue 9 2001Suzana P. Salcedo We used flow cytometry and confocal immunofluorescence microscopy to study the localization of Salmonella typhimurium in spleens of infected mice. Animals were inoculated intragastrically or intraperitoneally with S. typhimurium strains, constitutively expressing green fluorescent protein. Independently of the route of inoculation, most bacteria were found in intracellular locations 3 days after inoculation. Using a panel of antibodies that bound to cells of different lineages, including mononuclear phagocyte subsets, we have shown that the vast majority of S. typhimurium bacteria reside within macrophages. Bacteria were located in red pulp and marginal zone macrophages, but very few were found in the marginal metallophilic macrophage population. We have demonstrated that the Salmonella SPI-2 type III secretion system is required for replication within splenic macrophages, and that sifA, mutant bacteria are found within the cytosol of these cells. These results confirm that SifA and SPI-2 are involved in maintenance of the vacuolar membrane and intracellular replication in vivo. [source] Signaling pathways in innate immunityACTA OPHTHALMOLOGICA, Issue 2008A SALMINEN Inflammation has a key role in the pathogenesis of AMD. This lecture will review the recent progress in understanding the different host-defence mechanisms against pathogens and self-based danger signals involved in the activation of innate immunity. The innate defence system utilizes pattern recognition receptors (PRR) to respond to a variety of pathogen-associated (PAMP) and danger-associated (DAMP) molecular structures. Along with the well-known complement and scavenger receptor systems, Toll-like receptors (TLR) and NOD-like receptors (NLR) have also a crucial part in host-defence and these receptor systems can be activated both by PAMPs and DAMPs. Pattern recognition receptors are located either in cell surface, such as TLR2 and TLR4, or in intracellular locations, e.g. TLR3, TLR9 and all NLRs. PRRs show some specificity to ligands and also in downstream they activate different signaling pathways, most common of which are NF-kB and IRF-dependent pathways inducing inflammatory responses. Retinal pigment epithelial cells (RPE) have an important role in eye host-defence, both at apical and basolateral surfaces. Most of the TLRs are expressed in RPE cells, especially TLR3 and TLR4, and they can participate in photoreceptor outer segment recognition. TLR3 can also suppress angiogenesis. The functions of NLRs, e.g. those forming inflammasomes, are still unknown, although the danger-type of activation signals, such as oxidative stress and potassium efflux, are present in retinal pigment epithelium. It seems that the activation of innate immunity system via DAMPs and PRRs may have a central role in the pathogenesis of AMD. [source] | |||||||||||||