Biology subjects

Marquez, I.

Publications and source records attributed to Marquez, I..

5 recordsLinked to original sources

bioRxiv2024

The oncogene SLC35F2 is a high-specificity transporter for the micronutrients queuine and queuosine

The nucleobase queuine (q) and its nucleoside queuosine (Q) are micronutrients derived from bacteria that are acquired from the gut microbiome and/or diet in humans. Following cellular uptake, Q is incorporated at the wobble base (position 34) of tRNAs with a GUN anticodon, which is important for efficient translation. Early studies suggested that cytosolic uptake of queuine is mediated by a selective transporter that is regulated by mitogenic signals, but the identity of this transporter has remained elusive. Here, through a cross-species bioinformatic search and genetic validation, we have identified the solute carrier family member SLC35F2 as a unique transporter for both queuine and queuosine in Schizosaccharomyces pombe and Trypanosoma brucei. Furthermore, gene disruption in HeLa cells revealed that SLC35F2 is the sole transporter for queuosine in HeLa cells (Km 174 nM) and a high-affinity transporter for the queuine nucleobase (Km 67 nM), with the presence of another low-affinity transporter (Km 259 nM) in these cells. Competition uptake studies show that SLC35F2 is not a general transporter for other canonical ribonucleobases or ribonucleosides, but selectively imports q and Q. The identification of SLC35F2, an oncogene, as the transporter of both q and Q advances our understanding of how intracellular levels of queuine and queuosine are regulated and how their deficiency contributes to a variety of pathophysiological conditions, including neurological disorders and cancer. Significance StatementThe discovery of SLC35F2 as the eukaryotic transporter of queuine and queuosine is key to understanding how these micronutrients are salvaged from the human gut and distributed to different body tissues. Queuosine modification of tRNAs enhances the accuracy and efficiency of codon-anticodon pairing and regulates a range of biological and pathophysiological states, including oxidative stress responses, cancer, learning, memory, and gut homeostasis.

biochemistry↗

bioRxiv2024

Unveiling the role of yeast cytochrome c isoforms in the assembly of mitochondrial supercomplexes and the control of respiratory chain rate

Mitochondria play crucial roles as both the powerhouse and signaling center of cells, balancing cell survival and death to maintain homeostasis. Disruption of this balance can lead to various diseases. Therefore, exploring the components involved in mitochondrial metabolism presents a significant challenge. In this context, respiratory supercomplexes are evolutionarily conserved, stable associations between membrane complexes and molecules, including proteins and lipids, within the inner mitochondrial membrane. These supercomplexes dynamically respond to metabolic demands, enhancing the electron transfer rate and reducing the production of reactive oxygen species. Recent research has identified cytochrome c, a mobile electron carrier between complexes III and IV, as a potential key player in the formation of these supercomplexes. This study focuses on elucidating the role of cytochrome c in modulating the assembly of supercomplexes, using the yeast Saccharomyces cerevisiae as a model system for mitochondrial metabolism. Our findings indicate that the viability of Saccharomyces cerevisiae relies on the presence of cytochrome c, with both isoforms playing a role in the assembly of respiratory supercomplexes. Notably, isoform-2 of cytochrome c enhances electron transfer efficiency, resulting in reduced ROS production.

biophysics↗

bioRxiv2024

Concurrent predictive and prospective strategies in a simple visuomotor task

Interception, a fundamental visuomotor skill for activities such as driving and sports, involves two main strategies: predictive, anticipating the targets trajectory, and prospective, actively tracking and adjusting movement. Experimentally controlled factors could potentially influence the relative usage of these strategies. We designed a visuomotor task to probe the relationship between target predictability and interception strategies. We manipulated stimulus predictability through controlled adjustments of external forces, altering the targets trajectory. We also manipulated the availability of perceptual information by introducing spatial occlusion at specific parts of the visual field. Our observations indicate that decreased target variability promoted predictive interception, whereas increased variability prompted a shift toward prospective strategies. Notably, hand-catching trajectories exhibited increased curvature in response to changes in target variability, whereas eye trajectories displayed a relatively consistent curvature across trials. Similarly, heightened target variability resulted in delayed onset of hand movements while showing no discernible alterations in the onset of eye movements. Thus, gaze position was a poor predictor of hand position, highlighting distinct adaptive patterns for hand and eye movements in response to task unpredictability. Finally, participants exhibited consistent interception strategies within and across sessions, highlighting their differences and preferences for predictive or prospective strategies. These results reveal a dynamic interplay between target predictability and interception, suggesting a flexible combination of both approaches. Examining how humans integrate sensory information, plan, and execute movements provides a unique opportunity to characterize predictive and prospective interception strategies in dynamic, real-world scenarios.

neuroscience↗

bioRxiv2021

Surprise-induced enhancements in the associability of Pavlovian cues facilitate learning across behavior systems

Surprising violations of outcome expectancies have long been known to enhance the associability of Pavlovian cues; that is, the rate at which the cue enters into further associations. The adaptive value of such enhancements resides in promoting new learning in the face of uncertainty. However, it is unclear whether associability enhancements reflect increased associative plasticity within a particular behavior system, or whether they can facilitate learning between a cue and any arbitrary outcome, as suggested by attentional models of conditioning. Here, we show evidence consistent with the latter hypothesis. Violating the outcome expectancies generated by a cue in an appetitive setting (feeding behavior system) facilitated subsequent learning about the cue in an aversive setting (defense behavior system). In addition to shedding light on the nature of associability enhancements, our findings offer the neuroscientist a behavioral tool to dissociate their neural substrates from those of other, behavior system- or valence-specific changes. Moreover, our results present an opportunity to utilize associability enhancements to the advantage of counterconditioning procedures in therapeutic contexts.

animal behavior and cognition↗

bioRxiv2021

Agency rescues competition for credit assignment among predictive cues from adverse learning conditions

A fundamental assumption of learning theories is that the credit assigned to predictive cues is not simply determined by their probability of reinforcement, but by their ability to compete with other cues present during learning. This assumption has guided behavioral and neural science research for decades, and tremendous empirical and theoretical advances have been made identifying the mechanisms of cue competition. However, when learning conditions are not optimal (e.g., when training is massed), credit assignment is no longer competitive. This is a catastrophic failure of the learning system that exposes the individuals vulnerability to form spurious associations in the real world. Here, we uncover that cue competition can be rescued when conditions are suboptimal provided that the individual has agency over the learning experience. Our findings reveal a new connection between agency over learning and credit assignment to cues, and open new avenues of investigation into the underlying mechanisms.

animal behavior and cognition↗