Plant action: Multiple levels of regulation

This lecture is devoted to the relative contribution of various levels of regulation of the actin cytoskeleton functioning in the cell. Regulation at the levels of gene expression, mRNA and protein synthesis and stability, processes of actin polymerization/depolymerization and actin structures reorganization is briefly considered. Novel information about the pathways of signal transduction to the actin cytoskeleton with the involvement of Arp2/3 complex and RIC proteins is highlighted.     

NP7 protects from cell death induced by oxidative stress in neuronal and glial midbrain cultures from parkin null mice

Parkin mutations produce Parkinson’s disease (PD) in humans and nigrostriatal dopamine lesions related to increased free radicals in mice. We examined the effects of NP7, a synthetic, marine derived, free radical scavenger which enters the brain, on H₂O₂ toxicity in cultured neurons and glia from wild-type (WT) and parkin null mice (PK-KO).NP7, 5-10 μM, prevented the H₂O₂ induced apoptosis and necrosis of midbrain neuronal and glial cultures from WT and PK-KO mice. NP7 suppressed microglial activation and the H₂O₂ induced drop-out of dopamine neurons_. Furthermore, NP7 prevented the increased phosphorylation of ERK and AKT induced by H₂O₂. NP7 may be a promising neuroprotector against oxidative stress in PD.     

Oxygen: a master regulator of pancreatic development?

Beyond its role as an electron acceptor in aerobic respiration, oxygen is also a key effector of many developmental events. The oxygen‐sensing machinery and the very fabric of cell identity and function have been shown to be deeply intertwined. Here we take a first look at how oxygen might lie at the crossroads of at least two of the major molecular pathways that shape pancreatic development. Based on recent evidence and a thorough review of the literature, we present a theoretical model whereby evolving oxygen tensions might choreograph to a large extent the sequence of molecular events resulting in the development of the organ. In particular, we propose that lower oxygenation prior to the expansion of the vasculature may favour HIF (hypoxia inducible factor)‐mediated activation of Notch and repression of Wnt/β‐catenin signalling, limiting endocrine cell differentiation. With the development of vasculature and improved oxygen delivery to the developing organ, HIF‐mediated support for Notch signalling may decline while the β‐catenin‐directed Wnt signalling is favoured, which would support endocrine cell differentiation and perhaps exocrine cell proliferation/differentiation.     

The C-Terminal Domain of the mGluR1 Metabotropic Glutamate Receptor Affects Sensitivity to Agonists

Abstract: The metabotropic glutamate receptor (mGluR) subtype 1 exists as at least three variants (−1a, −1b, and −1c) generated by alternative splicing at the C-terminal domain. Fluorometric Ca²⁺ measurements were used to compare the concentration dependency of agonist-induced rises in intracellular free Ca²⁺ concentration ([Ca²⁺]_i) in human embryonic HEK 293 cells transiently expressing rat mGluR1a, mGluR1b, or mGluR1c. The rank order of agonist potencies was quisqualate ≫ (2 S, 1' S, 2' S )-2-(carboxycyclopropyl)glycine (L-CCG-I) > (1 S, 3 R )-1-aminocyclopentane-1,3-dicarboxylic acid [(1 S, 3 R )-ACPD] and did not differ among the splice variants. However, agonists were consistently more potent at mGluR1a than at mGluR1c and mGluR1b. In the same system, we characterized the agonist pharmacology of two chimeric rat mGluR3/1 receptors where the first and/or the second intracellular loop(s) and the C-terminal domain were exchanged with the corresponding mGluR1a or mGluR1c sequences and that were previously shown to mediate elevations in [Ca²⁺]_i in response to agonists. The potency of agonists was higher at the chimera having the C-terminus of mGluR1a as compared with those having the mGluR1c C-terminus. Both chimeric mGluR3/1 receptors had the same rank order of agonist potencies: L-CCG-I ≫ (1 S, 3 R )-ACPD ∼ quisqualate. These data support the hypothesis that the C-terminal domain of mGluRs plays a role in determining the potency of agonists for inducing mGluR-mediated functional responses.     

Treatment of HeLa cells with bacterial water extracts inhibits Shigella flexneri invasion

Abstract Pathogenesis mediated by Shigella flexneri requires invasion of the gastrointestinal epithelium. It has been previously shown that HeLa cells challenged with S. flexneri show alterations in their phosphotyrosine-containing protein profile. In this report, we demonstrated that bacterial water extracts (WE) abrogated the invasion of HeLa cells by S. flexneri in a dose-dependent manner. A proteinaceous component of S. flexneri was shown to be responsible for this inhibitory activity. Proteins encoded on the 140-MDa plasmid were not responsible for the observed inhibition. WE from other Gram-negative bacteria also inhibited Shigella invasion of HeLa cells. HeLa cells pretreated with WE showed changes in the profile and the intensity of phosphotyrosine-containing protein bands. These data were consistent with a surface protein component in WE which initiated aberrant host cell signaling at the membrane which may account for the inhibition of bacterial entry.     

Begging, food provisioning, and nestling competition in great tit broods infested with ectoparasites

Ectoparasites are a ubiquitous environmental component of breedingbirds, and it has repeatedly been shown that hematoph-agousectoparasites such as fleas and mites reduce the quality andnumber of offspring of bird hosts, thereby lowering the valueof a current brood. Selection acting on the hosts will favorphysiological and behavioral responses that will reduce theparasites' impact. However, the results of the few bird studiesthat addressed the question of whether parasitism leads to ahigher rate of food provisioning are equivocal, and the beggingresponse to infestation has rarely been quantified. A changein begging activity and parental rate of food provisioning couldbe predicted in either direction: parents could reduce theirinvestment in the brood in order to invest more in future broods,or they could increase their investment in order to compensatefor the parasites' effect on the current brood. Since the nestlingsare weakened by the ectoparasites they may beg less, but onthe other hand they may beg more in order to obtain more food.In this study we show experimentally that (1) hen fleas (Ceratophyllusgallinae) reduce the body mass and size of great tit (Parusmajor) nestlings, (2) nestlings of parasitized broods more thandouble their begging rate, (3) the male parents increase thefrequency of feeding trips by over 50%, (4) the females do notadjust feeding rate to the lowered nutritional state of nestlings,and (5) food competition among siblings of parasitized broodsis increased. Ultimately the difference in the parental feedingresponse may be understood as the result of a sex-related differencein the trade-off of i0vesting in current versus future broods.     

The importance of carotenoids in signaling during aggressive interactions between male firemouth cichlids (Cichlasoma meeki)

Male firemouth cichlids, Cichlasoma meeki, have red pigmentationcovering large areas of their ventral surface, which is displayedduring aggressive interactions. We manipulated the levels ofred pigmentation by assigning the fish to one of two diets,which were as similar as possible except that one was high incarotenoids while the other was low in carotenoids. During diadictrials under white light, fish kept on the high carotenoid dietwon a higher proportion of contests than fish kept on the lowcarotenoid diet Under green light, where differences in rednesscannot be discriminated, there was no effect of diet on theoutcome of contests. These experiments demonstrate that it isthe effect of the diet on red pigmentation that is importantrather than some confounding variable such as differential growthrates. The weight of the two fish was also important; therewas a tendency for the heavier fish to win more contests. Themass effect was subordinate to color under white light but wasthe dominant factor under green light The nature of the contestsunder the different light conditions also varied; the displayin which the red pigmentation is most obvious was not used undergreen light, but was common under white light This suggeststhat the display strategies are flexible and can be alteredaccording to which displays are most effective in a given environmentPrevious studies of other species of fish and birds have shownthat the degree of redness influences mate choice and is affectedby parasite infestations. We propose that carotenoid pigmentationis likely to reflect a general quality, influenced by severalfactors, rather than a context-specific quality such as fightingability.     

An experimental analysis of mate choice in the wren: a monomorphic, polygynous passerine

Male wrens (Troglodytes troglodytes) construct nests that areused in their display to females. Previous work has suggestedthat the number of vacant nests may be used as a mate choicecue. Correlational data from 1992 confirmed that females appearedto be assessing die number of vacant nests on a male's territoryand preferentially mating with males with more nests. Male taillengdi was also correlated widi mating success. In 1993 thenumbers of nests on territories was experimentally manipulated,the female setdement patterns confirmed that die number of vacantnests did mediate mate choice. Male tail length failed to explainadditional variance in mating success when die variance explainedby the experimental manipulation was removed, suggesting diatdie original correlation arose because both tail length andmating success were correlated widi a confounding variable.The structure of the vegetation in a male's territory influencedmating success. This appeared to be due to nests surviving betterin territories widi dense vegetation. Males on territories inwhich nests survive well had longer tails. Male-male competitionfor good territories may explain die observed effects of malemorphology on mating success. Furdier analysis of die nest choicedata showed diat all nests had an equal chance of being usedby a female. The fact diat all nests had an equal probabilityof being chosen by a female means diat each additional nestbuilt by a male wren results in die same increase in matingsuccess. This suggests diat die benefits to males of nest buildingincrease linearly. The number of nests on a territory will beaffected by various factors such as predation pressure, nestbuilding rate, and vegetation structure. The information diatfemales are getting by assessing such a signal is discussed.