Suizu, F. | bioRxiv Science

bioRxiv2023

Can Colpoda travel across oceans? Salinity tolerance of resting cysts may enable global dispersal of the species.

Protist species are distributed worldwide. The processes that enabled this global distribution are unclear. One possible means is through the oceanic dispersal of freshwater protists, although this has not been investigated in detail to date. Here, the ability of resting cysts to tolerate saline conditions is examined as a possible mechanism that enables the oceanic dispersal of protists. Resting cysts of Colpoda cucullus, a freshwater soil protist, can tolerate saline conditions of at least 3.5% NaCl for more than one week. A transcriptome analysis showed that the relative levels of expression of genes associated with membrane function are increased in resting cysts, indicating that salinity tolerance is associated with reconstruction of the cell membrane. Additionally, the outer layer of the cyst wall, a shell-like ectocyst, includes chitin. This may function as a form of "biological armor" that protects the cell from physical stress during oceanic dispersal. Teaser: Fresh water protists may be dispersed across oceans by formation of resting cysts that can tolerate saline conditions.

zoology↗

bioRxiv2022

AUTS2 gene dosage affects synaptic AMPA receptors via a local dendritic spine AUTS2-TTC3-AKT-mTORC1 signaling dysfunction

The Human 1.2-Mb AUTS2 locus on chromosome 7q11.22 encodes a 1259-aa full-length protein, and a 711-aa C-terminal isoform. Functions of these AUTS2 proteins are only partly known. The major traits found in patients displaying AUTS2 locus mutations are Intellectual Disabilities, microcephaly attention deficit hyperactivity disorder (ADHD) (54%), and autistic traits. Furthermore, AUTS2 common variants were recently found associated to alcohol consumption and dyslexia using GWAS approaches. Auts2 localizes mainly in cell nuclei. We evidenced by super-resolution that Auts2 is present in dendritic spines. Auts2 interacts with Ttc3, the Akt2 E3 ligase, and negatively regulates Akt2 ubiquitination. Auts2 haploinsufficiency affects Akt/mTorc1 pathway with a decrease in AMPA and NMDA receptor subunits and in synaptic currents. Akt2 injection in postsynaptic neurons is sufficient to reverse changes in synaptic currents generated by Auts2 haploinsufficiency. Using chromosome engineering based on targeted meiotic recombination, we generated two mouse models with Auts2 locus deletion and duplication. Deleted Auts2 locus mice display stereotypies (rearing), perseveration and abnormal recognition memory. Duplicated Auts2 locus mice display similar perseveration and abnormal recognition memory but also a decrease in cued and contextual fear memory. Gene dosage induce changes in brain sub-region neuronal networks. In the thalamo-lateral amygdala pathway linked to cued fear memory, we found synaptic impairments linked to AMPA receptors, with a specific decrease in pAKT/total AKT ratio in duplicated Auts2 mice. Altogether, our study thereby provides a novel mechanistic and potentially therapeutic understanding of synaptic AKT/mTORC1 deregulated signaling and its related behavioral and cognitive phenotypes.

neuroscience↗