PP2ACdc55 dephosphorylates Pds1 and inhibits spindle elongation in S. cerevisiae.

PP2ACdc55 (the form of protein phosphatase 2A containing Cdc55) regulates cell cycle progression by reversing cyclin-dependent kinase (CDK)- and polo-like kinase (Cdc5)-dependent phosphorylation events. In S. cerevisiae, Cdk1 phosphorylates securin (Pds1), which facilitates Pds1 binding and inhibits separase (Esp1). During anaphase, Esp1 cleaves the cohesin subunit Scc1 and promotes spindle elongation. Here, we show that PP2ACdc55 directly dephosphorylates Pds1 both in vivo and in vitro Pds1 hyperphosphorylation in a cdc55 deletion mutant enhanced the Pds1-Esp1 interaction, which played a positive role in Pds1 nuclear accumulation and in spindle elongation. We also show that nuclear PP2ACdc55 plays a role during replication stress to inhibit spindle elongation. This pathway acted independently of the known Mec1, Swe1 or spindle assembly checkpoint (SAC) checkpoint pathways. We propose a model where Pds1 dephosphorylation by PP2ACdc55 disrupts the Pds1-Esp1 protein interaction and inhibits Pds1 nuclear accumulation, which prevents spindle elongation, a process that is elevated during replication stress.

Exocrine Gland-Secreting Peptide 1 Is a Key Chemosensory Signal Responsible for the Bruce Effect in Mice.

The Bruce effect refers to pregnancy termination in recently pregnant female rodents upon exposure to unfamiliar males [1]. This event occurs in specific combinations of laboratory mouse strains via the vomeronasal system [2, 3]; however, the responsible chemosensory signals have not been fully identified. Here we demonstrate that the male pheromone exocrine gland-secreting peptide 1 (ESP1) is one of the key factors that causes pregnancy block. Female mice exhibited high pregnancy failure rates upon encountering males that secreted different levels of ESP1 compared to the mated male. The effect was not observed in mice that lacked the ESP1 receptor, V2Rp5, which is expressed in vomeronasal sensory neurons. Prolactin surges in the blood after mating, which are essential for maintaining luteal function, were suppressed by ESP1 exposure, suggesting that a neuroendocrine mechanism underlies ESP1-mediated pregnancy failure. The single peptide pheromone ESP1 conveys not only maleness to promote female receptivity but also the males' characteristics to facilitate memorization of the mating partner.

Lacrimal gland removal impairs sexual behavior in mice.

Exocrine gland-secreting peptides (ESPs) are a protein family involved in the pheromonal communication of rodents. ESP1 is a lacrimal peptide synthesized by the extraorbital glands of males of specific mouse strains that modulates the sexual behavior in females. Reportedly, BALB/c males, that produce high level of ESP1 in the tear fluid, were shown to enhance the lordosis behavior in C57BL/6 females during mating. In contrast, C57BL/6 and ICR males, both unable to express ESP1, failed to modulate this sexual behavior. Nonetheless, ICR males did become competent to enhance lordosis behavior in C57BL/6 females providing these were pre-exposed to ESP1. To exclude any strain differences, here, we investigated the pheromonal role of the extraorbital glands and indirectly of ESP1 in animals of the same strain. This was performed by applying the lordosis experimental paradigm in BALB/c mice before and after the surgical removal of these glands in males. The excision of the extraorbital glands reduced but did not abolish the production of ESP1 in the lacrimal fluid of BALB/c mice. An immunological analysis on soluble extracts of the glands that drain into the conjunctival sac revealed that the intraorbital glands (ILGs) are also responsible for the production of ESP1. The removal of both the extra and ILGs completely eliminated the tear secretion of ESP1. Extraorbital gland-deficient BALB/c mice were still able to induce lordosis behavior in sexually receptive females. In contrast, males with the removal of both the extra and ILGs failed to enhance lordosis behavior in females. Unexpectedly, C57BL/6 males did improve this sexual performance in BALB/c females. However, an analysis of the tear fluid of C57BL/6 males revealed low but detectable levels of ESP1. Overall, our study highlights the relevance of the orbital glands in modulating reproductive behavior and the sensitivity of the vomeronasal system to detect trace amount of ESP1.

Chemosensory signals and their receptors in the olfactory neural system.

Chemical communication is widely used among various organisms to obtain essential information from their environment required for life. Although a large variety of molecules have been shown to act as chemical cues, the molecular and neural basis underlying the behaviors elicited by these molecules has been revealed for only a limited number of molecules. Here, we review the current knowledge regarding the signaling molecules whose flow from receptor to specific behavior has been characterized. Discussing the molecules utilized by mice, insects, and the worm, we focus on how each organism has optimized its reception system to suit its living style. We also highlight how the production of these signaling molecules is regulated, an area in which considerable progress has been recently made.