Biology subjects

Watanabe, M.

Publications and source records attributed to Watanabe, M..

3 recordsLinked to original sources

bioRxiv2018

mitoNEET Regulates Mitochondrial Iron Homeostasis Interacting with Transferrin Receptor

Iron is an essential trace element for regulation of redox and mitochondrial function, and then mitochondrial iron content is tightly regulated in mammals. We focused on a novel protein localized at the outer mitochondrial membrane. Immunoelectron microscopy revealed transferrin receptor (TfR) displayed an intimate relationship with the mitochondria, and mass spectrometry analysis also revealed mitoNEET interacted with TfR in vitro. Moreover, mitoNEET was endogenously coprecipitated with TfR in the heart, which indicates that mitoNEET also interacts with TfR in vivo. We generated mice with cardiac-specific deletion of mitoNEET (mitoNEET-knockout). Iron contents in isolated mitochondria were significantly increased in mitoNEET-knockout mice compared to control mice. Mitochondrial reactive oxygen species (ROS) were higher, and mitochondrial maximal capacity and reserve capacity were significantly decreased in mitoNEET-knockout mice, which was consistent with cardiac dysfunction evaluated by echocardiography. The complex formation of mitoNEET with TfR may regulate mitochondrial iron contents via an influx of iron. A disruption of mitoNEET could thus be involved in mitochondrial ROS production by iron overload in the heart.

cell biology↗

bioRxiv2018

Conditional upregulation of KCC2 selectively enhances neuronal inhibition during seizures

Abstract/SummaryEfficacious neuronal inhibition is sustained by the neuronal K+Cl- co-transporter KCC2, and loss of KCC2 function through injury or mutation is associated with altered GABAergic signalling and neuronal seizures. Here we report a transgenic mouse with conditional KCC2 overexpression that results in increased membrane transport function. Increased KCC2 has little impact on behavioural and in vitro assays of neuronal excitability and GABAA receptor responses under resting conditions. In contrast, increased KCC2 imparts resistance to seizure-like neuronal activity in hippocampal slices and prevents the progression of mice into behavioural status epilepticus following multiple kainic acid doses. Our results demonstrate a transgenic mouse to facilitate investigations into the role of KCC2 in brain function, and provide a proof of principle that targeting KCC2 may be an effective way to selectively enhance neuronal inhibition to mitigate against diseases that involve an imbalance between excitation and inhibition.

neuroscience↗

bioRxiv2017

Dehydration Bouts Prompt Increased Activity And Blood Feeding By Mosquitoes

Mosquitoes are prone to dehydration and respond to this stress through multiple mechanisms, but previous studies have examined very specific responses and fail to provide an encompassing view of the role that dehydration has on mosquito biology. This study examined underlying changes in biology of the northern house mosquito, Culex pipiens, associated with short bouts of dehydration. We show that dehydration increased blood feeding propensity of mosquitoes, which was the result of both enhanced activity and a higher tendency to land on a host. Mosquitoes exposed to dehydrating conditions with access to water or rehydrated individuals experience no water loss and failed to display behavioral changes. RNA-seq and metabolome analyses following dehydration indicated that factors associated with energy metabolism are altered, specifically the breakdown of trehalose to yield glucose, which likely underlies changes in mosquito activity. Suppression of trehalose breakdown by RNA interference reduced phenotypes associated with dehydration. Comparable results were noted for two other mosquito species, suggesting this is a general response among mosquitoes. Lastly, field-based mesocosm studies using C. pipiens revealed that dehydrated mosquitoes were more likely to host feed, and disease modeling indicates dehydration bouts may increase transmission of West Nile virus. These results suggest that periods of dehydration prompt mosquitoes to utilize blood feeding as a mechanism to obtain water. This dehydration-induced increase in blood feeding is likely to intensify disease transmission during periods of low water availability.\n\nSignificanceDehydration stress has substantial impacts on the biology of terrestrial invertebrates. To date, no studies have elucidated the difference between dehydration exposure and realized water loss in relation to mosquito behavior and physiology. Our experiments show that direct dehydration stress increases mosquito activity and subsequent blood feeding, likely as a mechanism to locate and utilize a bloodmeal for rehydration. These dehydration-induced phenotypes were linked to altered carbohydrate metabolism that acts as a source of energy. This study provides important insight into the impact of mosquito-dehydration dynamics on disease transmission that is likely general among mosquitoes.

physiology↗