Search bioRxiv⌕ Search

Biology subjects

Yigit, E. N.

Publications and source records attributed to Yigit, E. N..

2 recordsLinked to original sources

Switching ON Hydrogen Sulfide: A Chemogenetic Toolkit for Spatially Resolved H2S Manipulation

Hydrogen sulfide (H2S) is emerging as a multifaceted signalling molecule that shapes energy metabolism, vascular tone, cancer biology and neurodegeneration. Although fluorescent and genetically encoded sensors now allow real-time H2S imaging, tools for selective control of intracellular H2S remain scarce. Here we benchmark two substrate-based chemogenetic enzymes--the yeast D-amino-acid oxidase (mDAAO) and the Salmonella typhimurium D-cysteine desulfhydrase (stDCyD)--for controlled H2S production. Both enzymes catalyse the conversion of D-cysteine to H2S, yet only mDAAO concomitantly generates hydrogen peroxide, introducing an unwanted oxidative signal. In contrast, stDCyD produces exclusively H2S, thereby offering a clean and efficient means to elevate intracellular H2S in vitro. Our data position stDCyD as the superior chemogenetic actuator for dissecting H2S biology without confounding redox artefacts.

biochemistry↗

Neurons protect themselves by active shrinkage upon axonal transection

Trauma, vascular events, or neurodegenerative processes can lead to axonal injury and eventual transection (axotomy). Neurons can survive axotomy, yet the underlying mechanisms are not fully understood. Excessive water entry into injured neurons poses a particular risk due to swelling and subsequent death. Using in vitro and in vivo neurotrauma model systems based on laser transection, we demonstrated that axotomy triggers actomyosin contraction coupled with calpain activity. As a consequence, neurons shrink acutely to force water out through aquaporin channels preventing swelling and bursting. Inhibiting shrinkage increased the probability of neuronal cell death by about three-fold. These studies reveal a previously unrecognized cytoprotective response mechanism to neurotrauma and offer a fresh perspective on pathophysiological processes in the nervous system. One-Sentence SummaryWhen the axon of a neuron is cut, its soma shrinks to pump out water to avoid deadly swelling.

neuroscience↗