Large-scale screen reveals how numerous signaling pathways intersect at the cell's primary protein-processing center

Apr 24, 2013
Large-scale screen reveals how numerous signaling pathways intersect at the cell’s primary protein-processing center
Many proteins undergo extensive processing and modification within the stacked compartments of the Golgi apparatus. Credit: iStockphoto/Thinkstock

Many proteins undergo extensive modification after being synthesized, particularly those that are secreted or embedded in the cell membrane. This is achieved within the Golgi apparatus (see image), a cellular organelle consisting of multiple membrane-bound compartments known as cisternae. Each of these contains specific sets of protein-modifying enzymes, which sequentially modify their targets. For example, many proteins undergo glycosylation, which entails the stepwise addition of complex sugar molecules.

Golgi function depends heavily on proper organization, particularly in . In an ambitious study, a research team led by Frederic Bard of the A*STAR Institute of has identified proteins that maintain this organelle's structure and function. Many critical cellular functions are managed by signaling enzymes that either add or remove phosphate chemical groups from , known respectively as kinases and phosphatases. Bard and co-workers focused on a set of 948 proteins encompassing most of these enzymes.

The researchers used a technique called to specifically reduce production of each protein in , and then applied a sophisticated imaging strategy to determine the impact on different subsets of Golgi cisternae. A series of pilot experiments using treatments known to affect Golgi function enabled them to 'train' their imaging software to recognize the physiological hallmarks associated with different disruptions. In parallel, Bard and co-workers applied a targeted fluorescent labeling strategy to 'color code' the various Golgi subcompartments, allowing them to determine which of these were specifically affected in each experiment.

Using the trained imaging algorithm, the researchers identified 159 signaling factors that apparently contribute to Golgi organization and structure. Many of these were directly linked to critical Golgi functions, such as the dynamic behavior of cisternal membranes or the trafficking system that physically shuttles molecules between cisternae. Several of the targets identified specifically transmit signals in response to extracellular cues, indicating that Golgi organization may be greatly affected by the environment outside of the cell.

Importantly, many of these signaling factors exert a particularly strong influence on glycosylation patterns. "The sheer complexity and diversity of glyco-phenotypes arising from signaling-gene depletion were very surprising," says Bard. Given that both signaling pathways and protein glycosylation are highly prone to disruption in cancerous cells, these data suggest that the Golgi could be an important nexus for some tumorigenic processes. Bard will explore this possibility in future work. "We plan to decipher the specific cascades of glycosylation regulation that are frequently activated in tumor cells," he says.

Explore further: Genomes of malaria-carrying mosquitoes sequenced

More information: Chia, J., Goh, G., Racine, V., Ng, S., Kumar, P. & Bard, F. RNAi screening reveals a large signaling network controlling the Golgi apparatus in human cells. Molecular Systems Biology 8, 629 (2012). www.nature.com/msb/journal/v8/… /full/msb201259.html

add to favorites email to friend print save as pdf

Related Stories

Stretching the Golgi: a link between form and function

Oct 15, 2009

A research team at the University of California, San Diego School of Medicine has provided a surprisingly simple explanation for the mechanism and features of the "Golgi apparatus" - a structure that has baffled ...

Researchers discover a protein that amplifies cell death

Jan 15, 2009

Scientists at Albert Einstein College of Medicine of Yeshiva University have identified a small intracellular protein that helps cells commit suicide. The finding, reported as the "paper of the week" in the ...

Surprising origin of cell's internal highways

Jun 20, 2007

Scientists have long thought that microtubules, part of the microscopic scaffolding that the cell uses to move things around in order to hold its shape and divide, originated from a tiny structure near the nucleus, called ...

Recommended for you

Genomes of malaria-carrying mosquitoes sequenced

Nov 27, 2014

Nora Besansky, O'Hara Professor of Biological Sciences at the University of Notre Dame and a member of the University's Eck Institute for Global Health, has led an international team of scientists in sequencing ...

How calcium regulates mitochondrial carrier proteins

Nov 26, 2014

Mitochondrial carriers are a family of proteins that play the key role of transporting a chemically diverse range of molecules across the inner mitochondrial membrane. Mitochondrial aspartate/glutamate carriers are part of ...

Team conducts unprecedented analysis of microbial ecosystem

Nov 26, 2014

An international team of scientists from the Translational Genomics Research Institute (TGen) and The Luxembourg Centre for Systems Biomedicine (LCSB) have completed a first-of-its-kind microbial analysis of a biological ...

Students create microbe to weaken superbug

Nov 25, 2014

A team of undergraduate students from the University of Waterloo have designed a synthetic organism that may one day help doctors treat MRSA, an antibiotic-resistant superbug.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.