Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein tags regulate key ion channel

08.04.2005


Newly recognized process solves 50-year-old mystery

Researchers at the University of Chicago have found that a recently discovered biological process known as sumoylation -- until now thought to be active only in the nucleus -- also occurs near the cell’s surface where it regulates at least one and possibly many kinds of proteins, providing a novel target for the development of new drugs.

The discovery, published in the 8 April 2005 issue of the journal Cell, answers a question dating back to the 1950s: How do cells control the background movement of potassium ions across the cell membrane? This process is important because the flow of potassium ions determines whether "excitable" cells in the brain, heart and skeletal muscles "fire," sending out nervous impulses that become thoughts, heartbeats and basketball dunks.



"We found that a little-studied process called sumoylation, previously associated with nuclear proteins, is active and essential outside the nucleus at the plasma membrane," said study author Steven Goldstein, M.D., Ph.D., professor and chairman of pediatrics and director of the Institute for Molecular Pediatric Sciences at the University of Chicago. "This adds a new chapter to the book of how cells control ion channel function: reversible peptide linkage."

Ion channels are in every cell in the human body. They are tightly controlled tunnels through the membrane barriers that hold in the cell’s contents, separating the cell from the outside world. Ion channels allow ions such as potassium, sodium and calcium to flow in and out and so are key regulators of many fundamental processes in biology. "Ions are the currency of the cellular world," explained Goldstein. "Cells collect some ions, others they discharge. Ions are stored, spent, and exchanged."

"Cellular solvency," he added, "the ability to respond to the stimuli that are life, is all about the balance between ions inside and outside each cell. The gradual doling out or sudden influx of ions through ion channels are the basis for those cellular activities that give us thoughts, sights, tastes, sounds and our ability to move."

"Consequently," he adds, "cells control these actions as carefully as we watch our finances, which is why so many of the most potent mediations we use to care for our patients’ target one or another ion channel." Goldstein’s team discovered the type of ion channel known as background (or leak) potassium channels in yeast cells in 1995 and in fruit flies in 1996. Although potassium leak was first described in the 1950s when it was recognized to control excitation of nerves, the reason for leak had not previously been understood.

The first human clone of this channel, K2P1, generated a good deal of excitement, Goldstein said, but no one could learn much about it because it always seemed to be mute. "This discouraged a lot of people."

The problem was that some hidden mechanism was silencing the channel, plugging the pipeline, but no known method of channel regulation seemed to be involved. Goldstein and colleagues began to suspect sumoylation [SUE-mow-e-LAY-shun]. In this process, an enzyme attaches a small peptide called SUMO (for small ubiquitin-like modifier protein) onto another protein. The presence of SUMO alters how the second protein functions.

Goldstein’s team first demonstrated that the SUMO-conjugating enzyme was plentiful at the plasma membrane, just inside the cell surface. They next showed that it added SUMO to a specific part of the K2P1 channel, and that when this happened the channel was entirely silent. When a different enzyme removed the SUMO tag, however, ions began to stream through the channel.

Understanding the role of sumoylation allowed the team to study the K2P1 channel for the first time. The channel is open at rest, the researchers found, and closed when the SUMO tag is attached. When it is closed, potassium ions build up within the cell. When they reach a threshold level, the cell is primed for activity, such as transmitting a nerve impulse.

Sumoylation has recently been recognized as an important mechanism of cellular activity but until now its 60-or-so known targets were primarily nuclear proteins, mostly involved in gene transcription. "The findings expand the influence of SUMO-related activity in biology," Goldstein said, "a great and exciting surprise." There is still a good deal that we don’t understand about this system, he said, "but now we know where to look and why we must go there. SUMO may very well act on other ion channels that have yet to reveal their function because they were silent like K2P1."

Other membrane proteins key to biology, like transporters and hormone receptors, may also be controlled by SUMO since the binding site is present in those proteins although not yet proven to operate. "Cells are fastidious in the way they regulate activity at their borders," Goldstein added. "Our work shows how sumoylation controls one important process at the cell surface and hints that it may influence others."

Additional authors include co-first authors Sindhu Rajan and Leigh Plant, as well as Michael Rabin and Margaret Butler, all from the Institute for Molecular Pediatric Sciences at the University of Chicago. "I am proud of the team," Goldstein emphasized. "They are remarkable collaborators, deeply dedicated and just plain smart."

John Easton | EurekAlert!
Further information:
http://www.uchospitals.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>