Distinct Molecular Events during Secretory Granule Biogenesis Revealed by Sensitivities to Brefeldin A

The biogenesis of peptide hormone secretory granules involves a series of sorting, modification, and trafficking steps that initiate in the trans-Golgi and trans-Golgi network (TGN). To investigate their temporal order and interrelationships, we have developed a pulse–chase protocol that follows the synthesis and packaging of a sulfated hormone, pro-opiomelanocortin (POMC). In AtT-20 cells, sulfate is incorporated into POMC predominantly on N-linked endoglycosidase H-resistant oligosaccharides. Subcellular fractionation and pharmacological studies confirm that this sulfation occurs at the trans-Golgi/TGN. Subsequent to sulfation, POMC undergoes a number of molecular events before final storage in dense-core granules. The first step involves the transfer of POMC from the sulfation compartment to a processing compartment (immature secretory granules, ISGs): Inhibiting export of pulse-labeled POMC by brefeldin A (BFA) or a 20°C block prevents its proteolytic conversion to mature adrenocorticotropic hormone. Proteolytic cleavage products were found in vesicular fractions corresponding to ISGs, suggesting that the processing machinery is not appreciably activated until POMC exits the sulfation compartment. A large portion of the labeled hormone is secreted from ISGs as incompletely processed intermediates. This unregulated secretory process occurs only during a limited time window: Granules that have matured for 2 to 3 h exhibit very little unregulated release, as evidenced by the efficient storage of the 15-kDa N-terminal fragment that is generated by a relatively late cleavage event within the maturing granule. The second step of granule biogenesis thus involves two maturation events: proteolytic activation of POMC in ISGs and a transition of the organelle from a state of high unregulated release to one that favors intracellular storage. By using BFA, we show that the two processes occurring in ISGs may be uncoupled: although the unregulated secretion from ISGs is impaired by BFA, proteolytic processing of POMC within this organelle proceeds unaffected. The finding that BFA impairs constitutive secretion from both the TGN and ISGs also suggests that these secretory processes may be related in mechanism. Finally, our data indicate that the unusually high levels of unregulated secretion often associated with endocrine tumors may result, at least in part, from inefficient storage of secretory products at the level of ISGs.

Airborne minerals and related aerosol particles: Effects on climate and the environment

Aerosol particles are ubiquitous in the troposphere and exert an important influence on global climate and the environment. They affect climate through scattering, transmission, and absorption of radiation as well as by acting as nuclei for cloud formation. A significant fraction of the aerosol particle burden consists of minerals, and most of the remainder— whether natural or anthropogenic—consists of materials that can be studied by the same methods as are used for fine-grained minerals. Our emphasis is on the study and character of the individual particles. Sulfate particles are the main cooling agents among aerosols; we found that in the remote oceanic atmosphere a significant fraction is aggregated with soot, a material that can diminish the cooling effect of sulfate. Our results suggest oxidization of SO2 may have occurred on soot surfaces, implying that even in the remote marine troposphere soot provided nuclei for heterogeneous sulfate formation. Sea salt is the dominant aerosol species (by mass) above the oceans. In addition to being important light scatterers and contributors to cloud condensation nuclei, sea-salt particles also provide large surface areas for heterogeneous atmospheric reactions. Minerals comprise the dominant mass fraction of the atmospheric aerosol burden. As all geologists know, they are a highly heterogeneous mixture. However, among atmospheric scientists they are commonly treated as a fairly uniform group, and one whose interaction with radiation is widely assumed to be unpredictable. Given their abundances, large total surface areas, and reactivities, their role in influencing climate will require increased attention as climate models are refined.

Possible forcing of global temperature by the oceanic tides

An approximately decadal periodicity in surface air temperature is discernable in global observations from A.D. 1855 to 1900 and since A.D. 1945, but with a periodicity of only about 6 years during the intervening period. Changes in solar irradiance related to the sunspot cycle have been proposed to account for the former, but cannot account for the latter. To explain both by a single mechanism, we propose that extreme oceanic tides may produce changes in sea surface temperature at repeat periods, which alternate between approximately one-third and one-half of the lunar nodal cycle of 18.6 years. These alternations, recurring at nearly 90-year intervals, reflect varying slight degrees of misalignment and departures from the closest approach of the Earth with the Moon and Sun at times of extreme tide raising forces. Strong forcing, consistent with observed temperature periodicities, occurred at 9-year intervals close to perihelion (solar perigee) for several decades centered on A.D. 1881 and 1974, but at 6-year intervals for several decades centered on A.D. 1923. As a physical explanation for tidal forcing of temperature we propose that the dissipation of extreme tides increases vertical mixing of sea water, thereby causing episodic cooling near the sea surface. If this mechanism correctly explains near-decadal temperature periodicities, it may also apply to variability in temperature and climate on other times-scales, even millennial and longer.

El Niño and the related phenomenon Southern Oscillation (ENSO): The largest signal in interannual climate variation

El Niño and the related phenomenon Southern Oscillation (ENSO) is the strongest signal in the interannual variation of ocean-atmosphere system. It is mainly a tropical event but its impact is global. ENSO has been drawing great scientific attention in many international research programs. There has been an observational system for the tropical ocean, and scientists have known the climatologies of the upper ocean, developed some theories about the ENSO cycle, and established coupled ocean-atmosphere models to give encouraging predictions of ENSO for a 1-year lead. However, questions remain about the physical mechanisms for the ENSO cycle and its irregularity, ENSO-monsoon interactions, long-term variation of ENSO, and increasing the predictive skill of ENSO and its related climate variations.