Proteins and peptides in Drosophila melanogaster seminal fluid induce mated females to increase their rates of egg deposition. One seminal-fluid protein, ovulin (Acp26Aa), stimulates an early step in the egg-laying process, the release of oocytes by the ovary. Ovulin, upon transfer to females, is cleaved sequentially within the mated female's reproductive tract. Here, we show that systemic ectopic expression of ovulin is sufficient to stimulate ovulation in unmated females. By using this assay to assess the functionality of ovulin's cleavage products, we find that two of the four cleavage products of ovulin can stimulate ovulation independently. Thus, ovulin's cleavage in mated females is not destructive and instead may liberate additional functional products with potential to modulate ovulation independently.mating ͉ processing ͉ prohormone ͉ seminal proteins E ven after mating, a male can continue to affect the reproductive success of his mate. One way this effect is accomplished results from the male's donation of seminal proteins. For example, in Drosophila melanogaster, Ϸ83 accessory gland proteins (Acps) are produced in the male's accessory glands (refs. 1 and 2; reviewed in ref.3). In the mated female, Acps increase egg production, ovulation, and egg deposition; decrease receptivity to remating; promote the storage of sperm; and decrease the lifespan of the mated female (reviewed in refs. 3-8). Individual Acps have been shown to cause specific changes in mated females: Acp26Aa (ovulin) and Acp70A (sex peptide) affect the egg-laying process (9-15), Acp70A affects receptivity (12-15), Acp36DE is needed for sperm storage (16,17), and Acp62F has been suggested to contribute to the decrease in the mated female's life span (18).Here, we focus on ovulin, an Acp that stimulates ovulation. Egg-laying in Drosophila is a multistep process (ref. 10; reviewed in ref. 19). First, eggs produced in the ovaries must pass checkpoints during oogenesis (refs. 20-22; reviewed in ref. 23). Mature oocytes are then released from ovaries (ovulation), a process that also triggers oocyte activation (24). Oocytes move through the oviducts to the uterus, where they can be fertilized by sperm released from storage, and, finally, they are released from the uterus and deposited onto the substratum (Fig. 1A). Mates of males who do not provide ovulin show decreased ovulation and egg deposition (9-11). Within the mated female, some ovulin from the male enters the circulatory system (hemolymph) and some localizes to the base of the ovary (10, 25). Thus, ovulin could conceivably induce ovulation in the female by direct interaction with neuromuscular targets along the upper region (lateral oviducts) of the genital tract or indirectly by affecting the activity of the neuroendocrine system (26).The sequence of ovulin suggests that it is a prohormone. The primary translation product is 264 aa long, including a predicted signal sequence of 18 aa that is expected to be cleaved to allow secretion of ovulin (27). Ovulin contains amino acid sequence...

No abstract

Improvement in care of epidermolysis bullosa in recent years results from keen clinical observation, novel molecular targeting, and the embracement of translational research.

Hypertension is a prevalent condition in the developed world and disease severity is directly correlated with additional cardiovascular complications. It is estimated that 30% of the adult population in the United States has hypertension, which is classified as a systolic blood pressure > or =140 mmHg and/or a diastolic blood pressure > or =90 mmHg. A prolonged increase in afterload ultimately leads to congestive heart failure in the majority of cases. Currently, medication designed to treat hypertension is inadequate, thus new therapies need to be explored. Blood pressure is tightly regulated by blood vessel radius, which is established by hormones and/or peptides binding to GPCRs (G-protein-coupled receptors). Catecholamines and peptide hormones, such as AngII (angiotensin II), are elevated in hypertension and, therefore, signalling by these GPCRs is increased. Their signalling is tightly controlled by a class of proteins, the GRKs (GPCR kinases). Elevated levels of either GRK2 or GRK5 in both the lymphocytes and VSM (vascular smooth muscle) are associated with human hypertension and animal models of the disease. The focus of the present review is on the role GRKs, and their regulation of GPCRs, play in high blood pressure.