Gabrielli, M. | bioRxiv Science

bioRxiv2021

Astrocytic extracellular vesicles modulate neuronal calcium homeostasis via transglutaminase-2

We have uncovered a novel role for astrocytes-derived extracellular vesicles (EVs) in controlling intraneuronal Ca2+ concentration ([Ca2+]i) and identified transglutaminase-2 (TG2) as a surface-cargo of astrocytes-derived EVs. Incubation of hippocampal neurons with primed astrocyte-derived EVs have led to an increase in [Ca2+]i, unlike EVs from TG2-knockout astrocytes. Exposure of neurons or brain slices to extracellular TG2 promoted a [Ca2+]i rise, which was reversible upon TG2 removal and was dependent on Ca2+ influx through the plasma membrane. Patch-clamp and calcium imaging recordings revealed TG2-dependent neuronal membrane depolarisation and activation of inward currents, due to the opening of L-type-VOCCs and to Na+/Ca2+ -exchanger (NCX) operation in the reverse mode, as indicated by VOCCs/NCX pharmacological inhibitors. A subunit of Na+/K+-ATPase was selected by comparative proteomics and identified as being functionally inhibited by extracellular TG2, implicating Na+/K+-ATPase inhibition in NCX reverse mode-switching leading to Ca2+ influx and higher basal [Ca2+]i. These data suggest that reactive astrocytes control intraneuronal [Ca2+]i through release of EVs with TG2 as responsible cargo, which could have a significant impact on synaptic activity in brain inflammation.

neuroscience↗

bioRxiv2018

A bird’s white-eye shot: looking down on a new avian sex chromosome evolution

AO_SCPCAPBSTRACTC_SCPCAPChromosomal organization is relatively stable among avian species, especially with regards to sex chromosomes. Members of the large Sylvioidea clade however have a pair of neo-sex chromosomes which is unique to this clade and originate from a parallel translocation of a region of the ancestral 4A chromosome on both W and Z chromosomes. Here, we took advantage of this unusual event to study the early stages of sex chromosome evolution. To do so, we sequenced a female (ZW) of two Sylvioidea species, a Zosterops borbonicus and a Z. pallidus. Then, we organized the Z. borbonicus scaffolds along chromosomes and annotated genes. Molecular phylogenetic dating under various methods and calibration sets confidently confirmed the recent diversification of the genus Zosterops (1-3.5 million years ago), thus representing one of the most exceptional rates of diversification among vertebrates. We then combined genomic coverage comparisons of five males and seven females, and homology with the zebra finch genome (Taeniopygia guttata) to identify sex chromosome scaffolds, as well as the candidate chromosome breakpoints for the two translocation events. We observed reduced levels of within-species diversity in both translocated regions and, as expected, even more so on the neoW chromosome. In order to compare the rates of molecular evolution in genomic regions of the autosomal-to-sex transitions, we then estimated the ratios of non-synonymous to synonymous polymorphisms ({pi}N/{pi}S) and substitutions (dN/dS). Based on both ratios, no or little contrast between autosomal and Z genes was observed, thus representing a very different outcome than the higher ratios observed at the neoW genes. In addition, we report significant changes in base composition content for translocated regions on the W and Z chromosomes and a large accumulation of transposable elements (TE) on the newly W region. Our results revealed contrasted signals of molecular evolution changes associated to these autosome-to-sex transitions, with congruent signals of a W chromosome degeneration yet a surprisingly weak support for a fast-Z effect.

evolutionary biology↗