Visualization Of Gα Proteins Using Super-Resolution Microscopy

Ono, Aiwa
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University of Hawaii at Manoa
Encoded by nearly 5% of the human genome, G protein-coupled receptors (GPCRs) comprise the largest superfamily of transmembrane proteins. They are involved in transducing an array of signals varying from molecular ligands (e.g. neurotransmitters and hormones) to sensory stimuli (e.g. odorants and photons) into cells via coupling with their partners—G proteins. Downstream signaling elicits a broad range of physiological functions, from growth to homeostasis regulation to the fight-or-flight responses. Such diversity explains why GPCRs have been targeted by nearly 50% of pharmaceutical drugs, including those targeting cardiac GPCRs that are prescribed for cardiovascular disease. Nevertheless, of all noncommunicable diseases, cardiovascular disease continues to be the leading cause of global morbidity and mortality; in 2008, it accounted for approximately one-third of all deaths according to the World Health Organization. Thus, there is a critical need to discover novel cardiovascular drugs and targets. This project focused on the very preliminary stage of this exploration, that is, to visualize G proteins using super-resolution microscopy. In the future, we will elucidate how the molecular distributions of G proteins on the mammalian plasma membrane contribute to GPCR activity in the cardiovascular system.
G protein-coupled receptor, G protein, photoactivatable green fluorescent protein, photoactivated localization microscopy
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