Biology subjects

Gonzalez-Recio, I.

Publications and source records attributed to Gonzalez-Recio, I..

3 recordsLinked to original sources

bioRxiv2025

Disruption of Reelin signaling in a dual-hit mouse model of schizophrenia: impact of postnatal Δ9-tetrahydrocannabinol exposure in a maternal immune activation model

Since the discovery of the first antipsychotic, pharmacological treatment of schizophrenia (SCZ) has primarily relied on agents that block D2 dopamine receptors. However, due to variability in patient responses, there is a pressing need to identify new biomarkers and therapeutic strategies. In this context, we have developed a dual-hit mouse model that combines maternal immune activation (MIA) induced by polyinosinic-polycytidylic acid (Poly(I:C)) and postnatal exposure to {Delta}9-tetrahydrocannabinol (THC), the psychoactive component of cannabis. We assessed the face validity of this model and investigated potential alterations in the Reelin signaling pathway. Our findings show a reduction in Reelin levels, a new potential key biomarker of SCZ, in the prefrontal cortex of male mice treated with THC compared to the dual-hit group, and across all treatment groups compared to controls in females. Additionally, a decrease in the number of Reelin+ cells was observed across these groups. The dual-hit model exhibited phenotypes indicative of positive symptoms in males, as well as phenotypes associated with negative symptoms in both sexes. Furthermore, the model demonstrated reduced cortical thickness in THC-treated groups, alongside decreased dendritic spine density in both the prefrontal cortex and hippocampus in the dual-hit group.

neuroscience↗

bioRxiv2021

Structure of Cystathionine β-Synthase from Toxoplasma gondii, a key enzyme in its H2S production machinery.

Cystathionine {beta}-synthase (CBS), the pivotal enzyme of the reverse transsulfuration pathway, catalyzes the pyridoxal-5-phosphate-dependent condensation of serine with homocysteine to form cystathionine. Additionally, CBS performs alternative reactions that use homocysteine and cysteine as substrates leading to the endogenous biosynthesis of hydrogen sulfide (H2S), an important signal transducer in many physiological and pathological processes. Toxoplasma gondii, the causative agent of toxoplasmosis, encodes a functional CBS (TgCBS) that contrary to human CBS, is not allosterically regulated by S-adenosylmethionine and can use both, Ser and O-acetylserine (OAS) as substrates. TgCBS is also strongly implicated in the production of H2S, and thus involved in redox homeostasis of the parasite. Here, we report its crystal structure, the first CBS from a protozoan described so far. Our data reveals a basal-like fold that unexpectedly differs from the active conformations found in other organisms, but structurally similar to the pathogenic activated mutant D444N of the human enzyme.

biochemistry↗

bioRxiv2020

ARL15 modulates magnesium homeostasis through N-glycosylation of CNNMs

Cyclin M (CNNM1-4) proteins maintain cellular and body magnesium (Mg2+) homeostasis. Using various biochemical approaches, we have identified members of the CNNM family as direct interacting partners of ADP-ribosylation factor-like protein 15 (ARL15), a small GTP-binding protein. ARL15 interacts with CNNMs at their carboxyl-terminal conserved cystathionine-{beta}-synthase (CBS) domains. In silico modeling of the interaction using the reported structures of both CNNM2 and ARL15 supports that the small GTPase specifically binds the CBS1 domain. Immunocytochemical experiments demonstrate that CNNM2 and ARL15 co-localize in the kidney, with both proteins showing subcellular localization in the Golgi-apparatus. Most importantly, we found that ARL15 is required for forming complex N-glycosylation of CNNMs. Overexpression of ARL15 promotes complex N-glycosylation of CNNM3. Mg2+ uptake experiments with a stable isotope demonstrate that there is a significant increase of 25Mg2+ uptake upon knockdown of ARL15 in multiple kidney cancer cell lines. Altogether, our results establish ARL15 as a novel negative regulator of Mg2+ transport by promoting the complex N-glycosylation of CNNMs.

biochemistry↗