We examined the possible occurrence and function of neuronal Ca2+ sensor 1 (NCS-1/frequenin) in the mast cell line rat basophilic leukemia, RBL-2H3. This protein has been implicated in the control of neurosecretion from dense core granules in neuronal cells as well as in the control of constitutive secretory pathways in both yeast and mammalian cells. We show that RBL-2H3 cells, secretory cells of the immune system, endogenously express the 22-kDa NCS-1 protein as well as an immune-related 50-kDa protein. Both proteins associate in vivo with phosphatidylinositol 4-kinase β (PI4Kβ) and colocalize with the enzyme in the Golgi region. We show further that overexpression of NCS-1 in RBL-2H3 cells stimulates the catalytic activity of PI4Kβ, increases IgE receptor (FcεRI)-triggered hydrolysis of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and stimulates FcεRI-triggered, but not Ca2+ ionophore-triggered, exocytosis. Conversely, expression of a kinase-dead mutant of PI4Kβ reduces PI4Kβ activity, decreases FcεRI-stimulated phosphatidylinositol 4,5-bisphosphate hydrolysis, and blocks FcεRI-triggered, but not Ca2+ ionophore-triggered, exocytosis. Our results indicate that PI(4)P, produced by the Golgi-localized PI4Kβ, is the rate-limiting factor in the synthesis of the pool of PI(4,5)P2 that serves as substrate for the generation of lipid-derived second messengers in FcεRI-triggered cells. We conclude that NCS-1 is involved in the control of regulated exocytosis in nonneural cells, where it contributes to stimulus-secretion coupling by interacting with PI4Kβ and positive regulation of its activity.
A three-level (individual, organizational and national) nursing marketing programme is proposed for implementation by nurse leadership and policy makers. Among proposed steps to improve marketing of the nursing profession are promotion of the image of nursing by the individual nurse in the course of her or his daily activities, formulation and implementation of policies and programmes to promote the image of nursing at the organizational level and drawing up of a long-term programme for promoting or marketing the professional status of nursing at the national level.
Veteran residents showed lower levels of knowledge about stroke. Educational campaigns aimed at increasing knowledge of stroke among Israel's general population in Israel, as well as culturally targeting specific subgroups, are recommended.
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