First View Of The Subcellular Human Proteome

Transmission electron microscope image of a thin section cut through an area of mammalian lung tissue. Credit: Louise Howard/Wikimedia Commons

Transmission electron microscope image of a thin section cut through an area of mammalian lung tissue. Credit: Louise Howard/Wikimedia Commons

Proteins are the workhorses of biology. These small molecular machines are involved in a vast array of essential functions including the transport of substances, copying of genetic material, speeding up chemical reactions in the cell, providing structural support, relaying messages in and between our cells, and are even involved in their own synthesis. The collection of all proteins expressed by the organism's genome is called the proteome (see image).  

Image credit: Sven Bulterijs

Image credit: Sven Bulterijs

Eukaryotic cells, as opposed to prokaryotic cells (i.e. the bacteria), have a very strongly organized interior that consists of several separate subcompartments called organelles. For example, the mitochondria are organelles responsible for energy production. This compartmentalization offers several benefits to the cell. For example, it allows the cell to isolate certain chemical reactions from the rest of the cell because they would otherwise conflict with other essential reactions. It also allows the cell to accumulate large amounts of a substance in an isolated bubble (a vesicle) that could be quickly released upon receiving the signal to do so. To better understand the way our cells work it is of paramount importance that we have a map of the subcellular localization of all proteins.     
 

Source: Wikimedia Commons  

Source: Wikimedia Commons
 

In a new study published in Science researchers report the result of a massive research project that lead to the subcellular mapping of over twelve thousand proteins in thirty subcellular structures. To accomplish this goal the researchers used over 13,000 antibodies to label the proteins and then collected over 80,000 microscopic images. To help process the floodgate of data the authors gamified the annotation of these microscopical images. More than 180,000 players contributed over 7 million minutes to date to annotate these images.       
 
Nearly simultaneously, another group reported a map of the tissue and subcellular proteome of the worm C. elegans. This worm is one of the most used model organisms in biomedical research and has contributed to key insights into the aging process. In contrast to the human study discussed above this study only differentiated two subcellular localizations (the nucleus and the cytoplasm) in four different tissues (intestines, ‘skin’, body wall muscle, and pharyngeal muscle). The method used in this study also differs from the one discussed above. The researchers took advantage of the tissue-specific and subcellular-location specific expression of an enzyme, not normally found in the worm, that chemically modifies proteins. In this way the authors were able to “tag” proteins which could then be selectively purified and analysed. This strategy lead to the successful creation of a localization map for over 3,000 proteins.  
 
Thul PJ et al. (2017). A subcellular map of the human proteome. Science 820(6340): eaal3321.  
 
Reinke AW et al. (2017). In vivo mapping of tissue- and subcellular-specific proteomes in Caenorhabditis elegans. Sci Adv 3: e1602426.