Synaptotagmin-2 controls regulated exocytosis but not other secretory responses of mast cells.

Mast cell degranulation is a highly regulated, calcium-dependent process, which is important for the acute release of inflammatory mediators during the course of many pathological conditions. We previously found that Synaptotagmin-2, a calcium sensor in neuronal exocytosis, was expressed in a mast cell line. We postulated that this protein may be involved in the control of mast cell-regulated exocytosis, and we generated Synaptotagmin-2 knock-out mice to test our hypothesis. Mast cells from this mutant animal conferred an abnormally decreased passive cutaneous anaphylaxis reaction on mast cell-deficient mice that correlated with a specific defect in mast cell-regulated exocytosis, leaving constitutive exocytosis and nonexocytic mast cell effector responses intact. This defect was not secondary to abnormalities in the development, maturation, migration, morphology, synthesis, and storage of inflammatory mediators, or intracellular calcium transients of the mast cells. Unlike neurons, the lack of Synaptotagmin-2 in mast cells was not associated with increased spontaneous exocytosis.

The effect of acculturation on diabetes prevalence in Hispanics: A systematic review

Context. The high prevalence of diabetes among Hispanics in the U.S. has stimulated increased interest in the role culture plays in Hispanics' risk of diabetes. It is critical to identify gaps in the existing research and to determine the relationship between acculturation and diabetes prevalence in the Hispanic population. ^ Objective. To review the current literature to evaluate the effects of acculturation on diabetes prevalence among Hispanic Americans. ^ Methods. A literature search of diabetes-related studies was conducted. Studies were selected for review if they reported at least one acculturation measure, used Hispanics adults (ages 18 and older) and included information regarding the diabetes prevalence of Hispanics and/or Latinos. Only those that examined acculturation by diabetes prevalence for Hispanics were included in the review. ^ Results. Sixteen studies were reviewed that met the search criteria and these studies used distinct measures of acculturation that captured four primary dimensions: time (duration of exposure to U.S. culture), language, culture and residence. Data represented studies conducted in a variety of settings, such as healthcare facilities in a state or region of the U.S. and nationally representative surveys. The data indicate positive, negative and no significant relationship with diabetes. Depending on the measure of acculturation used and gender the association between acculturation and diabetes varied. ^ Conclusions. There is no clear association between acculturation and diabetes prevalence; it can not be determined based on the available literature. Many of the studies examining this relationship found non-significant results and the directionality of the relationship varied greatly depending on the type of measure used, the number of measures used, and the study population. Ideal studies of acculturation should concentrate on investigating the links between time measures of acculturation, location of residence and changing beliefs, values and norms. A comprehensive acculturation scale is needed to better understand the complex relationship between diabetes prevalence amongst Hispanics and acculturation. ^

The Role of the Arched Helicases in Exosome-Mediated Function

RNA processing and degradation are two important functions that control gene expression and promote RNA fidelity in the cell. A major ribonuclease complex, called the exosome, is involved in both of these processes. The exosome is composed of ten essential proteins with only one catalytically active subunit, called Rrp44. While the same ten essential subunits make up both the nuclear and cytoplasmic exosome, there are nuclear and cytoplasmic exosome cofactors that promote specific exosome functions in each of the cell compartments. To date, it is unclear how the exosome distinguishes between RNA substrates. We hypothesize that compartment specific cofactors may promote the substrate specificity of the exosome. In this work, I characterize several cofactors of the exosome, both nuclear and cytoplasmic. First, I describe the arch domain, which is a unique domain in a nuclear and a cytoplasmic cofactor of the exosome. Specifically, I show that the arch domain of the nuclear exosome cofactor, Mtr4, is required for specific exosome-mediated activities and overlaps functionally with the exosome-associated exonuclease, Rrp6. Further, I show that the arch domain of Ski2 is required for the degradation of normal and aberrant mRNAs. Additionally, this work describes in detail the Mtr4 domains involved in the physical association with other RNA processing proteins. Further, I characterize the minimal Mtr4-binding region in a third exosome cofactor, Trf5. Understanding how exosome cofactors synergistically promote exosome function will provide us a better understanding of how the exosome complex precisely regulates its catalytic activities. As described here, cofactors play a major role in determining the substrate specificity of the nuclear and cytoplasmic exosome. Moreover, specific accessory domains, which are not involved in the catalytic function of the cofactor, are required for substrate targeting of the eukaryotic RNA exosome.