Store-operated Ca 2+ entry (SOCE) occurs in diverse cell types in response to depletion of Ca 2+ within the endoplasmic/sarcoplasmic reticulum and functions both to refill these stores and to shape cytoplasmic Ca 2+ transients. Here we report that in addition to conventional SOCE, skeletal myotubes display a physiological mechanism that we term excitation-coupled Ca 2+ entry (ECCE). ECCE is rapidly initiated by membrane depolarization. Like excitation-contraction coupling, ECCE is absent in both dyspedic myotubes that lack the skeletal muscle-type ryanodine receptor 1 and dysgenic myotubes that lack the dihydropyridine receptor (DHPR), and is independent of the DHPR l -type Ca 2+ current. Unlike classic SOCE, ECCE does not depend on sarcoplasmic reticulum Ca 2+ release. Indeed, ECCE produces a large Ca 2+ entry in response to physiological stimuli that do not produce substantial store depletion and depends on interactions among three different Ca 2+ channels: the DHPR, ryanodine receptor 1, and a Ca 2+ entry channel with properties corresponding to those of store-operated Ca 2+ channels. ECCE may provide a fundamental means to rapidly maintain Ca 2+ stores and control important aspects of Ca 2+ signaling in both muscle and nonmuscle cells.

The function of the flagellum-chemotaxis regulon requires the expression of many genes and is positively regulated by the cyclic AMP-catabolite activator protein (cAMP-CAP) complex. In this paper, we show that motile behavior was affected in Escherichia coli hns mutants. The loss of motility resulted from a complete lack of flagella. A decrease in the level of transcription of theflhD andfliA genes, which are both required for the synthesis of flagella, was observed in the presence of an hns mutation. Furthermore, the Fla-phenotype was not reversed to the wild type in the presence of a cfs mutation which renders the flagellum synthesis independent of the cAMP-CAP complex. These results suggest that the H-NS protein acts as a positive regulator of genes involved in the biogenesis of flagella by a mechanism independent of the cAMP-CAP pathway.In order to survive and develop in highly varied environments, microorganisms have to constantly monitor external conditions and respond to changes in pH, osmolarity, temperature, or chemicals. One of these adaptative behaviors causes motile bacteria to swim toward attractants (e.g., amino acids or carbohydrates) and away from repellents (e.g., alcohols and other toxic substances) in response to environmental cues.Bacterial motility is dependent on the presence of flagella. In Eschenichia coli, the biosynthesis of these multicomponent structures requires the expression of about 40 genes clustered at several regions on the chromosome. The transcription of the flagellar operons forms an ordered cascade in which the expression of genes located at a given level requires the transcription of another gene at an upper level. At the top of the hierarchy, the flhC and flhD genes constitute the master operon which controls the expression of all other flagellar genes (15,23).The expression of the master operon is sensitive to catabolite repression and is positively regulated by the cyclic AMPcatabolite activator protein (cAMP-CAP) complex (2, 4). Furthermore, the transcription of flagellar genes requires the DnaK, DnaJ, and GrpE heat shock proteins (29). The organization of the bacterial membrane is also known to affect swarming properties of E. coli. For example, flagellum formation is impaired in lipopolysaccharide (LPS)-deficient strains (17,26). Similarly, the pss mutation results in a drastic reduction in the membrane of phosphatidylethanolamine and in loss of flagellation (27) (20) and is under negative autoregulation in the exponential growth phase (7,8,30). In E. coli, mutations at the hns locus are highly pleiotropic and are known to affect the expression of several apparently unrelated genes (6, 10, 33).We have previously described the isolation of pleiotropic hns mutants of E. coli. These strains showed an increased resistance to kanamycin in the presence of plasmid pGR71 (5, 21). In contrast, an increased susceptibility to chloramphenicol was observed in the hns mutants, in spite of similar chloramphenicol acetyltransferase activities in wild-type and mutant strains (21). Th...

Presently, co-culture of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) with BV2 microglia under amyloid-β42 (Aβ42) exposure induced a reduction of Aβ42 in the medium as well as an overexpression of the Aβ-degrading enzyme neprilysin (NEP) in microglia. Cytokine array examinations of co-cultured media revealed elevated release of soluble intracellular adhesion molecule-1 (sICAM-1) from hUCB-MSCs. Administration of human recombinant ICAM-1 in BV2 cells and wild-type mice brains induced NEP expression in time- and dose-dependent manners. In co-culturing with BV2 cells under Aβ42 exposure, knockdown of ICAM-1 expression on hUCB-MSCs by small interfering RNA (siRNA) abolished the induction of NEP in BV2 cells as well as reduction of added Aβ42 in the co-cultured media. By contrast, siRNA-mediated inhibition of the sICAM-1 receptor, lymphocyte function-associated antigen-1 (LFA-1), on BV2 cells reduced NEP expression by ICAM-1 exposure. When hUCB-MSCs were transplanted into the hippocampus of a 10-month-old transgenic mouse model of Alzheimer's disease for 10, 20, or 40 days, NEP expression was increased in the mice brains. Moreover, Aβ42 plaques in the hippocampus and other regions were decreased by active migration of hUCB-MSCs toward Aβ deposits. These data suggest that hUCB-MSC-derived sICAM-1 decreases Aβ plaques by inducing NEP expression in microglia through the sICAM-1/LFA-1 signaling pathway.