Year: 2017
Type: article
Abstract: Adduction of an electrophile to privileged sensor proteins and the resulting phenotypically dominant responses are increasingly appreciated as being essential for metazoan health. Functional similarities between the biological electrophiles and electrophilic pharmacophores commonly found in covalent drugs further fortify the translational relevance of these small-molecule signals. Genetically encodable or small-molecule-based fluorescent reporters and redox proteomics have revolutionized the observation and profiling of cellular redox states and electrophile-sensor proteins, respectively. However, precision mapping between specific redox-modified targets and specific responses has only recently begun to be addressed, and systems tractable to both genetic manipulation and on-target redox signaling in vivo remain largely limited. Here we engineer transgenic Caenorhabditis elegans expressing functional HaloTagged fusion proteins and use this system to develop a generalizable light-controlled approach to tagging a prototypical electrophile-sensor protein with native electrophiles in vivo. The method circumvents issues associated with low uptake/distribution and toxicity/promiscuity. Given the validated success of C. elegans in aging studies, this optimized platform offers a new lens with which to scrutinize how on-target electrophile signaling influences redox-dependent life span regulation.
Source: Biochemistry
Authors: Marcus J. C. Long, Daniel A. Urul, Shivansh Chawla, Hong-Yu Lin, Yi Zhao, Joseph A. Haegele, Yiran Wang, Yimon Aye
Institutions: Cornell University, Weill Cornell Medicine
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: G1134277896, G1734629682, G2004869984, G2318728625, G3452294746, G4147293139, G4378667772, G4504108201, Chemistry of Biological Systems, G4989108295, G5151707659, G5986892838, G6671297155, CAREER: A Chemical Technology to Define Target-Specific Bioreactivity: Integrating Research and Education at the Crossroads of Chemistry and Biology, Deconvoluting Redox Biology with Targeted Chemistry, Graduate Research Fellowship Program (GRFP), MRI: Acquisition of a Cryogenic Probe and Modern Console for Outstanding NMR Sensitivity to Benefit Research and Education at Cornell University, Zeiss LSM710 Confocal Microscope for Shared Imaging Facility, G8229174675, G8389919011, G8876996369
OpenAlex ID: W2752904899