Study identifies critical 'traffic engineer' of the nervous system

Sep 08, 2010
In this image, mammalian cells are labeled with an antibody that reveals microtubules, which serve as tracks for the shuttling of materials from one part of the cell to another. A new University of Georgia study published in the journal Nature has identified a critical enzyme that keeps traffic flowing in the right direction in the microtubules of nervous system cells. Credit: Dorota Wloga/University of Georgia

A new University of Georgia study published in the journal Nature has identified a critical enzyme that keeps traffic flowing in the right direction in the nervous system, and the finding could eventually lead to new treatments for conditions such as Alzheimer's and Parkinson's disease.

"There was no medical or any other applied science drive for this project; it was purely curiosity about how transport inside cells works," said study co-author Jacek Gaertig, professor in the cellular biology department in the UGA Franklin College of Arts and Sciences. "But it looks like we have identified an important that acts in the ."

He explained that cells contain a network of tubes known as microtubules that are made of protein and serve as tracks for the shuttling of materials from one part of the cell to another. The traffic signs on this microtubule network are chemical additions such as acetylation marks. Microtubules in parts of in the brain that send signals, for example, are loaded with acetylation marks. Microtubules in parts of neurons that receive signals, on the other hand, have few.

Acetylation marks were discovered in 1983, and researchers recently determined their role in regulating the binding of the motor proteins that shuttle materials along microtubules. What has been unclear for more than 25 years, however, was the cellular process by which these acetylation marks are formed. In other words, which enzyme decides where the traffic signs go?

Through a series of studies using the microscopic protozoan Tetrahymena, the C. elegans, and human cancer cells, Gaertig and his colleagues revealed that an a protein known as MEC-17 is the traffic engineer in charge of microtubule acetylation.

MEC-17 acts as an enzyme to catalyze the acetylation reaction on microtubules, and is involved in the sensation of touch in the nematode. Its depletion in zebrafish, which are commonly used as a to study basic processes, results in neuromuscular defects. Importantly, several research groups have previously reported that the levels of acetylation marks on microtubules are altered in human neurodegenerative diseases such as Huntington's, Parkinson's and Alzheimer's.

Gaertig said that with the enzyme identified and its mechanism of action known, it is now possible for drug manufacturers to search for compounds that block or enhance its activity.

Graduate student Shilpa Akella and postdoctoral associate Dorota Wloga in Gaertig's lab studied the enzyme in the protozoan and in vitro, while Jihyun Kim and Natalia Starostina in the lab of Edward Kipreos, professor of cellular biology, showed how it worked in the nematode and found that the enzyme is active in human cancer cells. The lab of associate professor and Georgia Cancer Coalition Distinguished Scholar Scott Dougan deduced its role in zebrafish, and Sally Lyons-Abbott and Naomi Morrissette at the University of California-Irvine biochemically purified that are marked by MEC-17.

"Working together allowed us to use all kinds of models to establish that this microtubule acetylation process using MEC-17 is an evolutionarily conserved function," Gaertig said. "Without close collaboration, that would not have been possible."

Explore further: mTORC pathway involved in antiphospholipid sx vasculopathy

Related Stories

Scientists locate disease switches

Jul 17, 2009

A team of scientists from the University of Copenhagen and the Max Planck Institute in Germany, has identified no less than 3,600 molecular switches in the human body. These switches, which regulate protein functions, may ...

One-dimensional Diffusion Accelerates Molecular Motors

May 12, 2006

Max Planck scientists have identified a new strategy which motor proteins use to move. The research was carried out by Prof. Jonathon Howard and Stefan Diez at the Max Planck Institute of Molecular Cell Biology ...

Roadworks on the motorways of the cell

Dec 28, 2006

A cell is a busy place. In a permanent rush hour, molecules are transported along a dynamic motorway system made up of filaments called microtubules. Microtubules constantly grow and shrink and are rapidly ...

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

Strategy proposed for preventing diseases of aging

15 hours ago

Medicine focuses almost entirely on fighting chronic diseases in a piecemeal fashion as symptoms develop. Instead, more efforts should be directed to promoting interventions that have the potential to prevent ...

User comments : 0