RUN and FYVE domain–containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4

Autophagy is a key degradative pathway coordinated by external cues, including starvation, oxidative stress, or pathogen detection. Rare are the molecules known to contribute mechanistically to the regulation of autophagy and expressed specifically in particular environmental contexts or in distinct cell types. Here, we unravel the role of RUN and FYVE domain–containing protein 4 (RUFY4) as a positive molecular regulator of macroautophagy in primary dendritic cells (DCs). We show that exposure to interleukin-4 (IL-4) during DC differentiation enhances autophagy flux through mTORC1 regulation and RUFY4 induction, which in turn actively promote LC3 degradation, Syntaxin 17–positive autophagosome formation, and lysosome tethering. Enhanced autophagy boosts endogenous antigen presentation by MHC II and allows host control of Brucella abortus replication in IL-4–treated DCs and in RUFY4-expressing cells. RUFY4 is therefore the first molecule characterized to date that promotes autophagy and influences endosome dynamics in a subset of immune cells.     

CUX2 Protein Functions as an Accessory Factor in the Repair of Oxidative DNA Damage

CUX1 and CUX2 proteins are characterized by the presence of three highly similar regions called Cut repeats 1, 2, and 3. Although CUX1 is ubiquitously expressed, CUX2 plays an important role in the specification of neuronal cells and continues to be expressed in postmitotic neurons. Cut repeats from the CUX1 protein were recently shown to stimulate 8-oxoguanine DNA glycosylase 1 (OGG1), an enzyme that removes oxidized purines from DNA and introduces a single strand break through its apurinic/apyrimidinic lyase activity to initiate base excision repair. Here, we investigated whether CUX2 plays a similar role in the repair of oxidative DNA damage. Cux2 knockdown in embryonic cortical neurons increased levels of oxidative DNA damage. In vitro, Cut repeats from CUX2 increased the binding of OGG1 to 7,8-dihydro-8-oxoguanine-containing DNA and stimulated both the glycosylase and apurinic/apyrimidinic lyase activities of OGG1. Genetic inactivation in mouse embryo fibroblasts or CUX2 knockdown in HCC38 cells delayed DNA repair and increased DNA damage. Conversely, ectopic expression of Cut repeats from CUX2 accelerated DNA repair and reduced levels of oxidative DNA damage. These results demonstrate that CUX2 functions as an accessory factor that stimulates the repair of oxidative DNA damage. Neurons produce a high level of reactive oxygen species because of their dependence on aerobic oxidation of glucose as their source of energy. Our results suggest that the persistent expression of CUX2 in postmitotic neurons contributes to the maintenance of genome integrity through its stimulation of oxidative DNA damage repair.     

Selfish male‐determining element favors the transition from hermaphroditism to androdioecy

According to the current, widely accepted paradigm, the evolutionary transition from hermaphroditism toward separate sexes occurs in two successive steps: an initial, intermediate step in which unisexual individuals, male or female, sterility mutants coexist with hermaphrodites and a final step that definitively establishes dioecy. Two nonexclusive processes can drive this transition: inbreeding avoidance and reallocation of resources from one sexual function to the other. Here, we report results of controlled crosses between males and hermaphrodites in Phillyrea angustifolia, an androdioecious species with two mutually intercompatible, but intraincompatible groups of hermaphrodites. We observed different segregation patterns that can be explained by: (1) epistatic interactions between two unlinked diallelic loci, determining sex and mating compatibility, and (2) a mutation with pleiotropic effects: female sterility, full compatibility of males with both hermaphrodite incompatibility groups, and complete male‐biased sex‐ratio distortion in one of the two groups. Modeling shows that these mechanisms can explain the high frequency of males in populations of P. angustifolia and can promote the maintenance of androdioecy without requiring inbreeding depression or resource reallocation. We thus argue that segregation distortion establishes the right conditions for the evolution of cryptic dioecy and potentially initiates the evolution toward separate sexes.     

The dynamics of coexistence: habitat sharing versus segregation patterns among three sympatric montane vipers

Contact zones of closely related and ecologically similar species constitute rare opportunities to study the evolutionary consequences of past speciation processes. They represent natural laboratories in which strong competition could lead to the exclusion of one species, or the various species may switch into distinct ecological niches. Alternatively, if reproductive isolation has not yet been achieved, they may hybridize. We elucidate the degree of taxon integrity by comparing genetics and habitat use of three similar‐sized congeneric viper species, Vipera ammodytes, Vipera aspis, and Vipera berus, of Nadiza Valley in western Slovenia. No hybridization was detected for either mitochondrial or nuclear genomes. Similarly, external intermediacy by a single prestudy viper (probably V. ammodytes × V. aspis) indicates that hybridization occasionally occurs, but should be very rare. Populations of the three related viperids are partially allopatric in Nadiza Valley, but they also coexist in a narrow contact zone in the montane grassland along the south‐exposed slope of Mount Stol (1673 m a.s.l.). Here, the three species that occupy areas in or near patches of rocky microhabitats (e.g. stone piles, slides, and walls) live in syntopy. However, fine‐scale measurements of structural components show partial habitat segregation, in which V. berus becomes more dominant at elevations above 1400 m and occupies mostly the mountain ridge and north‐exposed slopes of Mount Stol, V. aspis occurs below 1300 m and is the only species to inhabit stoneless patches of grass and bushes around 1000 m and lower, and V. ammodytes occurs at all elevations up to 1500 m, but is restricted to a rocky microhabitat. We suggest that a high degree of microstructure divergence, slightly different environmental niches, and a generally favourable habitat for all three viper species, keep the pressure for mis‐mating and hybridization low, although mechanisms such as reduced hybrid inferiority and temporal mating segregation cannot yet be excluded.     

Phylogeny and systematics of mitriform gastropods (Mollusca: Gastropoda: Neogastropoda)

With about 800 Recent species, ‘miters’ are a widely distributed group of tropical and subtropical gastropods that are most diverse in the Indo‐West Pacific. They include the two families Mitridae and Costellariidae, similar in shell morphology and traditionally treated as close relatives. Some genera of deep‐water Ptychatractidae and Volutomitridae are close to miters in shell morphology, and the term ‘mitriform gastropods’ has been introduced to refer to Mitridae, Costellariidae, and this assortment of convergent forms. The present study aimed at the reconstruction of phylogenetic relationships of mitriform gastropods based on representative taxon sampling. Four genetic markers [cytochrome c oxidase subunit I (COI), 16S and 12S rRNA mitochondrial genes, and H3 (Histone 3) nuclear gene] were sequenced for over 90 species in 20 genera, and the molecular data set was supplemented by studies of radula morphology. Our analysis recovered Mitridae as a monophyletic group, whereas the genus Mitra was found to be polyphyletic. Of 42 mitrid species included in the analysis, 37 formed a well‐supported ‘core Mitridae’ consisting of four major clades, three of them consistent with the subfamilies Cylindromitrinae, Imbricariinae, and Mitrinae, and Strigatella paupercula standing out by itself. Basal to the ‘core Mitridae’ are four minor lineages, with the genus Charitodoron recognized as sister group to all other Mitridae. The deep‐water family Pyramimitridae shows a sister relationship to the Mitridae, with high support for a Pyramimitridae + Mitridae clade. Our results recover the monophyly of the Costellariidae, which form a well‐supported clade that also includes Ptychatractidae, Columbariinae, and Volutomitridae, but not Mitridae. Most derived and diverse amongst Costellariidae are species of Vexillum, characterized by a bow‐shaped, multicuspidate rachidian tooth. Several previously unrecognized deep‐water costellariid lineages are revealed. Their members retain some plesiomorphies – in particular a tricuspidate rachidian tooth – that makes them morphologically intermediate between ptychatractids and Vexillum. The taxa of Ptychatractidae included in the analysis are not monophyletic, but form three well‐supported, unrelated groupings, corresponding respectively to Ceratoxancus + Latiromitra, Exilia, and Exiliodea. None of them shows an affinity to Pseudolividae. © 2015 The Linnean Society of London     

The EF-Hand Ca2+ Binding Protein MICU Choreographs Mitochondrial Ca2+ Dynamics in Arabidopsis

Plant organelle function must constantly adjust to environmental conditions, which requires dynamic coordination. Ca²⁺ signaling may play a central role in this process. Free Ca²⁺ dynamics are tightly regulated and differ markedly between the cytosol, plastid stroma, and mitochondrial matrix. The mechanistic basis of compartment-specific Ca²⁺ dynamics is poorly understood. Here, we studied the function of At-MICU, an EF-hand protein of Arabidopsis thaliana with homology to constituents of the mitochondrial Ca²⁺ uniporter machinery in mammals. MICU binds Ca²⁺ and localizes to the mitochondria in Arabidopsis. In vivo imaging of roots expressing a genetically encoded Ca²⁺ sensor in the mitochondrial matrix revealed that lack of MICU increased resting concentrations of free Ca²⁺ in the matrix. Furthermore, Ca²⁺ elevations triggered by auxin and extracellular ATP occurred more rapidly and reached higher maximal concentrations in the mitochondria of micu mutants, whereas cytosolic Ca²⁺ signatures remained unchanged. These findings support the idea that a conserved uniporter system, with composition and regulation distinct from the mammalian machinery, mediates mitochondrial Ca²⁺ uptake in plants under in vivo conditions. They further suggest that MICU acts as a throttle that controls Ca²⁺ uptake by moderating influx, thereby shaping Ca²⁺ signatures in the matrix and preserving mitochondrial homeostasis. Our results open the door to genetic dissection of mitochondrial Ca²⁺ signaling in plants.     

A mechanism of leading-edge protrusion in the absence of Arp2/3 complex

Cells employ protrusive leading edges to navigate and promote their migration in diverse physiological environments. Classical models of leading-edge protrusion rely on a treadmilling dendritic actin network that undergoes continuous assembly nucleated by the Arp2/3 complex, forming ruffling lamellipodia. Recent work demonstrated, however, that, in the absence of the Arp2/3 complex, fibroblast cells adopt a leading edge with filopodia-like protrusions (FLPs) and maintain an ability to move, albeit with altered responses to different environmental signals. We show that formin-family actin nucleators are required for the extension of FLPs but are insufficient to produce a continuous leading edge in fibroblasts lacking Arp2/3 complex. Myosin II is concentrated in arc-like regions of the leading edge in between FLPs, and its activity is required for coordinated advancement of these regions with formin-generated FLPs. We propose that actomyosin contraction acting against membrane tension advances the web of arcs between FLPs. Predictions of this model are verified experimentally. The dependence of myosin II in leading-edge advancement helps explain the previously reported defect in directional movement in the Arpc3-null fibroblasts. We provide further evidence that this defect is cell autonomous during chemotaxis.     

Seasonally different response of photosynthetic activity to daytime and night‐time warming in the Northern Hemisphere

Over the last century the Northern Hemisphere has experienced rapid climate warming, but this warming has not been evenly distributed seasonally, as well as diurnally. The implications of such seasonal and diurnal heterogeneous warming on regional and global vegetation photosynthetic activity, however, are still poorly understood. Here, we investigated for different seasons how photosynthetic activity of vegetation correlates with changes in seasonal daytime and night‐time temperature across the Northern Hemisphere (>30°N), using Normalized Difference Vegetation Index (NDVI) data from 1982 to 2011 obtained from the Advanced Very High Resolution Radiometer (AVHRR). Our analysis revealed some striking seasonal differences in the response of NDVI to changes in day‐ vs. night‐time temperatures. For instance, while higher daytime temperature (T_max) is generally associated with higher NDVI values across the boreal zone, the area exhibiting a statistically significant positive correlation between T_max and NDVI is much larger in spring (41% of area in boreal zone – total area 12.6 × 10⁶ km²) than in summer and autumn (14% and 9%, respectively). In contrast to the predominantly positive response of boreal ecosystems to changes in T_max, increases in T_max tended to negatively influence vegetation growth in temperate dry regions, particularly during summer. Changes in night‐time temperature (T_min) correlated negatively with autumnal NDVI in most of the Northern Hemisphere, but had a positive effect on spring and summer NDVI in most temperate regions (e.g., Central North America and Central Asia). Such divergent covariance between the photosynthetic activity of Northern Hemispheric vegetation and day‐ and night‐time temperature changes among different seasons and climate zones suggests a changing dominance of ecophysiological processes across time and space. Understanding the seasonally different responses of vegetation photosynthetic activity to diurnal temperature changes, which have not been captured by current land surface models, is important for improving the performance of next generation regional and global coupled vegetation‐climate models.     

Could the acid–base status of Antarctic sea urchins indicate a better‐than‐expected resilience to near‐future ocean acidification?

Increasing atmospheric carbon dioxide concentration alters the chemistry of the oceans towards more acidic conditions. Polar oceans are particularly affected due to their low temperature, low carbonate content and mixing patterns, for instance upwellings. Calcifying organisms are expected to be highly impacted by the decrease in the oceans' pH and carbonate ions concentration. In particular, sea urchins, members of the phylum Echinodermata, are hypothesized to be at risk due to their high‐magnesium calcite skeleton. However, tolerance to ocean acidification in metazoans is first linked to acid–base regulation capacities of the extracellular fluids. No information on this is available to date for Antarctic echinoderms and inference from temperate and tropical studies needs support. In this study, we investigated the acid–base status of 9 species of sea urchins (3 cidaroids, 2 regular euechinoids and 4 irregular echinoids). It appears that Antarctic regular euechinoids seem equipped with similar acid–base regulation systems as tropical and temperate regular euechinoids but could rely on more passive ion transfer systems, minimizing energy requirements. Cidaroids have an acid–base status similar to that of tropical cidaroids. Therefore Antarctic cidaroids will most probably not be affected by decreasing seawater pH, the pH drop linked to ocean acidification being negligible in comparison of the naturally low pH of the coelomic fluid. Irregular echinoids might not suffer from reduced seawater pH if acidosis of the coelomic fluid pH does not occur but more data on their acid–base regulation are needed. Combining these results with the resilience of Antarctic sea urchin larvae strongly suggests that these organisms might not be the expected victims of ocean acidification. However, data on the impact of other global stressors such as temperature and of the combination of the different stressors needs to be acquired to assess the sensitivity of these organisms to global change.