First genome-wide assessment of secretion in human cells

Jun 04, 2012
First genome-wide assessment of secretion in human cells

(Phys.org) -- An international collaboration between scientists in University College Dublin and the European Molecular Biology Laboratory (EMBL) has revealed for the first time that 15% of the proteins encoded by the human genome contribute to the process of secretion in cells. This finding has been made possible through the assessment of more than 8 million individual cells.

“This study is the first genome-wide assessment of the secretory process in a human cell system”, explains Professor Jeremy Simpson, UCD School of Biology & Environmental Science and UCD Conway Institute, co-author of the research paper published online today in Nature Cell Biology.

Science has long recognised that is a fundamental process, essential to almost all cell types in the body. The process is used to deliver hormones into the blood stream, digestive enzymes into the gut, and signalling molecules between .

However, until now, technology did not permit scientists to catalogue the complex pathway that a protein or lipid takes from manufacture to packaging and transporting through the cell to being secreted from the cell.

“Previous studies on the secretory process have either been carried out with a more narrow focus on specific subsets of genes or in more simplistic organisms such as the fruit fly (Drosophila) where many of the proteins identified have no human equivalent. Now, using high content screening, we have been able to systematically target each of the 22,000 human genes and track the journey of a specific, fluorescently-tagged protein as it travels through, and out of, over 8 million individual cells.”

“In order for us to understand the impact on the body when this fundamental process of secretion is disrupted, we must first decipher the functional network of membrane trafficking pathways within the cell.”

The researchers analysed more than 700,000 microscopy images and found 554 proteins that influence secretion, with 143 of these either influencing the early stage of the secretory pathway or morphology of the Golgi, a cellular structure responsible for packaging and labelling proteins.

Membrane traffic pathways connect membrane bound organelles in a carefully ordered sequence that ensures the correct complement of proteins and lipids within the cell exist in order to maintain cellular balance or homeostasis.

Image caption: In cells where different genes are silenced (middle, bottom), the site where the secretory processes begins (green) changes compared to normal cells (top). Courtesy of Jeremy Simpson, UCD

Newly synthesized proteins and lipids in the endoplasmic reticulum (ER) are modified as they pass along the secretory pathway through the Golgi apparatus to the cell surface.

The secretory pathway has the capacity to cope with a wide variety of cargo molecules, and as such utilises extensive regulatory machinery in the process. This study focuses on particular regulatory elements in the early stage of the pathway called the cytoplasmic coat complexes.  

This work was carried out in collaboration with co-author Dr. Rainer Pepperkok and Dr. Jan Ellenberg from EMBL, Heidelberg. The major part of funding for this research has come from Science Foundation Ireland, the EU-funded network of excellence, ‘Systems Microscopy’, and the EU-FP6 MitoCheck consortium.

Explore further: Nanocrystalline cellulose modified into an efficient viral inhibitor

More information: Simpson, J.C., et al. Genome-wide RNAi screening identifies human proteins with a regulatory function in the early secretory pathway. Nature Cell Biology, Advance Online Publication 3 June 2012. DOI: 10.1038/ncb2510

Related Stories

Scientists map one of life's molecular mysteries

Jan 26, 2012

All living organisms are made up of cells, behind these intricate life forms lie complex cellular processes that allow our bodies to function. Researchers working on protein secretion — a fundamental process in biology ...

Lending a helping hand

Jul 15, 2011

Many proteins, the primary building blocks of life, depend on elements such as copper, zinc and other trace elements to function properly. “Some metal molecules are required as a structural component ...

Researchers ID molecular link key for cell growth

Jan 24, 2011

(PhysOrg.com) -- When a cell is preparing to grow or replicate, it starts the way a monarch planning to expand his territory might: by identifying and marshaling the necessary resources, loading them onto ...

Recommended for you

Lifestyle determines gut microbes

17 hours ago

An international team of researchers has for the first time deciphered the intestinal bacteria of present-day hunter-gatherers.

Rethink education to fuel bioeconomy, says report

19 hours ago

Microbes can be highly efficient, versatile and sophisticated manufacturing tools, and have the potential to form the basis of a vibrant economic sector. In order to take full advantage of the opportunity microbial-based ...

User comments : 0

More news stories

Gene removal could have implications beyond plant science

(Phys.org) —For thousands of years humans have been tinkering with plant genetics, even when they didn't realize that is what they were doing, in an effort to make stronger, healthier crops that endured climates better, ...

Making 'bucky-balls' in spin-out's sights

(Phys.org) —A new Oxford spin-out firm is targeting the difficult challenge of manufacturing fullerenes, known as 'bucky-balls' because of their spherical shape, a type of carbon nanomaterial which, like ...