Plasmodium berghei leucine-rich repeat protein 1 downregulates protein phosphatase 1 activity and is required for efficient oocyst development

Protein phosphatase 1 (PP1) is a key enzyme for Plasmodium development. However, the detailed mechanisms underlying its regulation remain to be deciphered. Here, we report the functional characterization of the Plasmodium berghei leucine-rich repeat protein 1 (PbLRR1), an orthologue of SDS22, one of the most ancient and conserved PP1 interactors. Our study shows that PbLRR1 is expressed during intra-erythrocytic development of the parasite, and up to the zygote stage in mosquitoes. PbLRR1 can be found in complex with PbPP1 in both asexual and sexual stages and inhibits its phosphatase activity. Genetic analysis demonstrates that PbLRR1 depletion adversely affects the development of oocysts. PbLRR1 interactome analysis associated with phospho-proteomics studies identifies several novel putative PbLRR1/PbPP1 partners. Some of these partners have previously been characterized as essential for the parasite sexual development. Interestingly, and for the first time, Inhibitor 3 (I3), a well-known and direct interactant of Plasmodium PP1, was found to be drastically hypophosphorylated in PbLRR1-depleted parasites. These data, along with the detection of I3 with PP1 in the LRR1 interactome, strongly suggest that the phosphorylation status of PbI3 is under the control of the PP1–LRR1 complex and could contribute (in)directly to oocyst development. This study provides new insights into previously unrecognized PbPP1 fine regulation of Plasmodium oocyst development through its interaction with PbLRR1.     

Lithium Effects on Inositol Phospholipids and Inositol Phosphates: Evaluation of an In Vivo Model for Assessing Polyphosphoinositide Turnover in Brain

Administration of lithium chloride to rats injected intracerebrally with [3H]inositol led to time- and dose-dependent increases in levels of labeled inositol monophosphates in brain. Quantitative analysis of the inositol phosphates by ion chromatography revealed 37- and 20-fold increases in the mass of myo-inositol 1-phosphate and 4-phosphate, respectively, at 4 h intraperitoneal after injections of 6 mEq/kg of lithium chloride. Albeit to a much lesser extent, lithium administration also resulted in an increase in the level of myo-inositol, 1,4-bisphosphate in brain. The lithium-induced increase in content of labeled inositol monophosphates was marked by a concomitant decrease in content of labeled inositol, and after injections of high doses of lithium, e.g., 10 mEq/kg, this was followed by a general decrease in labeling of the inositol phospholipids. In general, animals injected with [3H]inositol but not lithium did not reveal obvious differences in labeling of inositol monophosphates on stimulation by mecamylamine or pilocarpine. However, when animals were injected with [3H]inositol and then lithium, there were large increases in the levels of labeled inositol monophosphates on administration of these compounds. Administration of atropine to the lithium-treated mice led to a partial reduction in the amount of labeled inositol monophosphates accumulated due to the administration of lithium alone. Furthermore, atropine was able to block the pilocarpine-induced increase in level of labeled inositol monophosphates. These results demonstrate the suitable use of the radiotracer technique together with lithium administration for assessing the effects of drugs and receptor agonists on the signaling system involving polyphosphoinositide turnover in brain.     

Males of the predatory mirid bug Macrolophus caliginosus exploit plant volatiles induced by conspecifics as a sexual synomone

The olfactory responses of male and female Macrolophus caliginosus Wagner (Heteroptera: Miridae) adults towards volatiles from green bean plants previously exposed to feeding by conspecifics and to direct odours from conspecifics were tested in a Y-tube olfactometer. Female M. caliginosus did not respond to volatiles from plants exposed to mirid feeding or to odours emitted directly by adult mirids. In contrast, male mirid bugs were attracted both to volatiles from plants previously exposed to feeding by conspecific females and to odours emitted by conspecifics only with a marginally significant preference for the former. The gas chromatography-mass spectrometry analysis showed that mirid feeding induced the release of 11 additional compounds as compared to the volatiles emitted from clean plants. Three of these substances (5-ethyl-2(5H)-furanone, Z-3-hexenyl tiglate, and E,E-α-farnesene) were released only after feeding by females. Furthermore, 21 compounds were identified in volatiles emitted directly by mirids, 12 of which were unique to the mirids (i.e., not present in clean plants or plants previously exposed to mirid feeding). The results suggest that female-specific herbivore-induced plant volatiles play a role as mate-finding cues by the male mirids. The ecological implications of the findings are discussed, and the term ‘sexual synomone’ is introduced.     

Loss of STOP Protein Impairs Peripheral Olfactory Neurogenesis

Background

STOP (Stable Tubulin-Only Polypeptide) null mice show behavioral deficits, impaired synaptic plasticity, decrease in synaptic vesicular pools and disturbances in dopaminergic transmission, and are considered a neurodevelopmental model of schizophrenia. Olfactory neurons highly express STOP protein and are continually generated throughout life. Experimentally-induced loss of olfactory neurons leads to epithelial regeneration within two months, providing a useful model to evaluate the role played by STOP protein in adult olfactory neurogenesis.

Methodology/Principal Findings

Immunocytochemistry and electron microscopy were used to study the structure of the glomerulus in the main olfactory bulb and neurogenesis in the neurosensorial epithelia. In STOP null mice, olfactory neurons showed presynaptic swellings with tubulovesicular profiles and autophagic-like structures. In olfactory and vomeronasal epithelia, there was an increase in neurons turnover, as shown by the increase in number of proliferating, apoptotic and immature cells with no changes in the number of mature neurons. Similar alterations in peripheral olfactory neurogenesis have been previously described in schizophrenia patients. In STOP null mice, regeneration of the olfactory epithelium did not modify these anomalies; moreover, regeneration resulted in abnormal organisation of olfactory terminals within the olfactory glomeruli in STOP null mice.

Conclusions/Significance

In conclusion, STOP protein seems to be involved in the establishment of synapses in the olfactory glomerulus. Our results indicate that the olfactory system of STOP null mice is a well-suited experimental model (1) for the study of the mechanism of action of STOP protein in synaptic function/plasticity and (2) for pathophysiological studies of the mechanisms of altered neuronal connections in schizophrenia.     

A biochemical study on the level of lipids and glycoproteins in the serum and platelets of liver cirrhotic bleeders

Bleeding complication and abnormal platelet functions are associated with liver cirrhosis. The aim of the present investigation was to assess the functional integrity of platelets in terms of lipids like cholesterol and phospholipids, glycoproteins and membrane-bound enzymes. Liver cirrhotic patients with bleeding complications were studied. Age and sex matched normal healthy volunteers were also involved in this study as a control group. Levels of cholesterol, phospholipids, glycoproteins and adenosine triphosphatases were assessed in isolated platelet membrane fraction. The level of glycoproteins and the activity of adenosine triphosphatases were found to be decreased significantly in cirrhotic patients. The cholesterol/phospholipid ratio was found to be altered significantly, indicating an alteration in the fluidity of platelet membrane. The results of this study reveal that the functional impairment of platelets in liver cirrhotic patients which is responsible for their bleeding tendency might also be due to altered lipid and enzyme levels in platelet membrane.