Featured Research

from universities, journals, and other organizations

New type of protein action found to regulate development

Date:
April 24, 2014
Source:
Johns Hopkins Medicine
Summary:
Researchers report they have figured out how the aptly named protein Botch blocks the signaling protein called Notch, which helps regulate development. In a report on the discovery, the scientists say they expect the work to lead to a better understanding of how a single protein, Notch, directs actions needed for the healthy development of organs as diverse as brains and kidneys.

Brain cells were engineered to produce fluorescent green Botch protein in the developing mouse cortex. Nuclei of cells are in blue.
Credit: Zhikai Chi

Johns Hopkins researchers report they have figured out how the aptly named protein Botch blocks the signaling protein called Notch, which helps regulate development. In a report on the discovery, to appear online April 24 in the journal Cell Reports, the scientists say they expect the work to lead to a better understanding of how a single protein, Notch, directs actions needed for the healthy development of organs as diverse as brains and kidneys.

The Johns Hopkins team says their experiments show that Botch uses a never-before-seen mechanism, replacing one chemical group with another that physically blocks the action of another enzyme. "We knew that Botch regulated Notch, and now we know it has its own novel way of getting the job done," says Valina Dawson, Ph.D., professor of neuroscience in the Johns Hopkins University School of Medicine's Institute for Cell Engineering, who led the study. "What's surprising is that Botch doesn't pull from the usual toolkit of enzymatic mechanisms."

Notch is, in fact, a family of four proteins with nearly identical properties and actions in mice and men. The proteins, Dawson says, dwell in the membranes surrounding cells, where they act as receptors, responding to specific signals outside of the cells by starting a chain reaction of signals inside. "There's a laundry list of things Notch does, from getting stem cells to develop into different organs to helping produce red blood cells," Dawson says. "The big question is how a seemingly simple signaling system could have such different effects."

The research team led by Dawson and her husband and collaborator, Ted Dawson, M.D., Ph.D., discovered Botch while looking for proteins that could protect the brain from injury. Since it was a newly found protein, they looked for answers on how Botch functions by finding other proteins with which it could interact, and that resulted in discovering Notch.

After Notch emerges from one of the cell's protein manufacturing centers, several things have to happen before it can go to work in the cell membrane. One of these is the addition of the chemical group glycine to a specific part of the protein. After that, an enzyme called furin cuts Notch near the glycine site. Botch removes the glycine from the spot where furin cuts. More surprisingly, Valina Dawson says, Botch then replaces the glycine with another chemical group that blocks furin from getting to the cut site. "Researchers are used to seeing enzymes change other proteins' function through common mechanisms, like adding or subtracting a phosphate group," Dawson says. "But Botch uses a tactic that no one has reported seeing before: It lops off glycine and adds a chemical structure called 5-oxy-proline."

Now that scientists know what to look for, they'll likely be able to identify other enzymes that use the same trick, Dawson says, and Botch itself may turn out to have other target proteins. Knowing how Botch works on Notch contributes to scientists' understanding of the biochemistry of development. It may also have implications for the treatment of some leukemias that have been linked to a mutation in the area of Notch close to the Botch-targeted glycine, Dawson adds.


Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Zhikai Chi, SeanT. Byrne, Andrew Dolinko, MagedM. Harraz, Min-Sik Kim, George Umanah, Jun Zhong, Rong Chen, Jianmin Zhang, Jinchong Xu, Li Chen, Akhilesh Pandey, TedM. Dawson, ValinaL. Dawson. Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch. Cell Reports, 2014; DOI: 10.1016/j.celrep.2014.03.048

Cite This Page:

Johns Hopkins Medicine. "New type of protein action found to regulate development." ScienceDaily. ScienceDaily, 24 April 2014. <www.sciencedaily.com/releases/2014/04/140424125142.htm>.
Johns Hopkins Medicine. (2014, April 24). New type of protein action found to regulate development. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2014/04/140424125142.htm
Johns Hopkins Medicine. "New type of protein action found to regulate development." ScienceDaily. www.sciencedaily.com/releases/2014/04/140424125142.htm (accessed October 21, 2014).

Share This



More Plants & Animals News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

White Lion Cubs Born in Belgrade Zoo

White Lion Cubs Born in Belgrade Zoo

AFP (Oct. 20, 2014) Two white lion cubs, an extremely rare subspecies of the African lion, were recently born at Belgrade Zoo. They are being bottle fed by zoo keepers after they were rejected by their mother after birth. Duration: 00:42 Video provided by AFP
Powered by NewsLook.com
Traditional Farming Methods Gaining Ground in Mali

Traditional Farming Methods Gaining Ground in Mali

AFP (Oct. 20, 2014) He is leading a one man agricultural revolution in Mali - Oumar Diatabe uses traditional farming methods to get the most out of his land and is teaching others across the country how to do the same. Duration: 01:44 Video provided by AFP
Powered by NewsLook.com
Goliath Spider Will Give You Nightmares

Goliath Spider Will Give You Nightmares

Buzz60 (Oct. 20, 2014) An entomologist stumbled upon a South American Goliath Birdeater. With a name like that, you know it's a terrifying creepy crawler. Sean Dowling (@SeanDowlingTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Adorable Video of Baby Rhino and Lamb Friend Playing

Adorable Video of Baby Rhino and Lamb Friend Playing

Buzz60 (Oct. 20, 2014) Gertjie the Rhino and Lammie the Lamb are teaching the world about animal conservation and friendship. TC Newman (@PurpleTCNewman) has the adorable video! Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins