Abstract
Localizing specific proteins within cells, tissues, and organisms has been a goal of microscopists for generations. In the early 1990s, a breakthrough was made when a molecule originally derived from a jellyfish was introduced as a probe for fluorescence microscopy. This molecule is green fluorescent protein (GFP), and it has become well known for its usefulness in localizing proteins at the level of the light microscope. It is also well known that electron microscopy (EM) offers far superior spatial resolution over light microscopy, but the application of probes to localize specific proteins has required antibodies conjugated with colloidal metals (such as gold). Delivery of antibodies into the cell commonly requires detergents to permeabilize the cell membrane, which compromises the ultrastructural detail. Another breakthrough was recently published on-line by Xiaokun Shu, Varda Lev-Ram, Thomas Deerinck, Yingchuan Qi, Ericka Ramko, Michael Davidson, Yishi Jin, Mark Ellisman, and Roger Tsien: they have developed a method similar to using GFP for light microscopy, but for specifically tagging proteins at the EM level.
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