Biology subjects

Zuniga, D.

Publications and source records attributed to Zuniga, D..

2 recordsLinked to original sources

bioRxiv2024

Biochemical, biophysical, and structural investigations of two mutants (C154Y and R312H) of the human Kir2.1 channel involved in the Andersen-Tawil syndrome.

Inwardly rectifying potassium (Kir) channels play a pivotal role in physiology by establishing, maintaining, and regulating the resting membrane potential of the cells, particularly contributing to the cellular repolarization of many excitable cells. Dysfunction in Kir2.1 channels is implicated in several chronic and debilitating human diseases for which there are currently no effective treatments. Specifically, Kir2.1-R312H and Kir2.1-C154Y mutations are associated with Andersen-Tawil syndrome (ATS) in humans. We have investigated the impact of these two mutants in the trafficking of the channel to the cell membrane and function in Xenopus laevis oocytes. Despite both mutations being successfully trafficked to the cell membrane and capable of binding PIP2 (phosphatidylinositol-4,5- bisphosphate), the main modulator for channel activity, they resulted in defective channels that do not display K+ current, albeit through different molecular mechanisms. Co-expression studies showed that R312H and C154Y are expressed and associated with the WT subunits. While WT subunits could rescue R312H dysfunction, the presence of a unique C154Y subunit disrupts the function of the entire complex, which is a typical feature of mutations with a dominant-negative effect. Molecular dynamics simulations showed that Kir2.1-C154Y mutation induces a loss in the structural plasticity of the selectivity filter, impairing the K+ flow. In addition, the cryo-EM structure of the Kir2.1-R312H mutant has been reconstructed. This study identified the molecular mechanisms by which two ATS-causing mutations impact Kir2.1 channel function and provide valuable insights that can guide potential strategies for the development of future therapeutic interventions for ATS.

biophysics↗

bioRxiv2023

The physiological costs of spatial positioning and leadership in collective movements

Individuals can gain substantial benefits from collective actions1-7. However, collective behaviours introduce new challenges, like coordinating actions, maintaining cohesion, and meeting the needs of different individuals. When making collective movements, leaders are typically thought to gain disproportionate benefits through the choice of more beneficial resources3 and/or earlier access to resources8. However, reaping these benefits can also have costs. Being at the front of a group can increase physical exertion4,9,10 and predation risk11,12. Moreover, ending up in a leadership position (i.e., at the front), is a process of negotiation in many animal groups. Within-group differences in directional preferences are typically resolved by some individuals initiating directional movements, after which they are either followed (if they are successful in leading) or return to the group (if they fail)13-30. By combining data on movement initiations (using whole-group GPS tracking31 and individual heart rate from implanted ECG loggers) in wild vulturine guineafowl, we found significant increases in heart rate (and decreases in heart rate variability) during collective movements. We found that attempting--and failing--to initiate directional movement was particularly costly, with the highest costs when consensus among group members was low and when individuals acted against the majority. Increases in heart rate and decreases in its variability can indicate physiological stress, entailing increased energy expenditure and long-term physiological damage. These results suggest that behaviours often thought beneficial to individuals (by influencing group behaviours) are also physiologically costly, representing a constraint on group-living and explaining why sometimes individuals opt out of contributing to leadership.

ecology↗