Featured Research

from universities, journals, and other organizations

A Protein-Processing Program Plays A Role In Cell Signaling

Date:
March 1, 2000
Source:
Washington University School Of Medicine
Summary:
Scientists have discovered a new way in which cells can relay messages to affect gene activity. They have evidence that cell membranes serve as chop shops for dismantling proteins into fragments that can act as messengers to change cell behavior.

St. Louis, Feb. 25, 2000 — Scientists have discovered a new way in which cells can relay messages to affect gene activity. They have evidence that cell membranes serve as chop shops for dismantling proteins into fragments that can act as messengers to change cell behavior.

"There might be a whole array of events occurring at the cell surface or at internal membranes that are regulated in this way," says Raphael Kopan, Ph.D., associate professor of medicine and molecular biology & pharmacology at Washington University School of Medicine in St. Louis. Kopan led a study on the processing of the developmental protein Notch that will be published in today's Molecular Cell. His findings corroborate those of scientists who have studied proteins that regulate lipid metabolism, the folding of new proteins and other processes.

In a May 1998 article in Nature, Kopan and his colleagues revealed that a fragment of Notch serves as a messenger that determines a cell's fate. Notch, a protein found inserted in the outer membrane of cells, has a part that juts out in the cell's surroundings and another that juts into the interior of the cell. The part that sticks out serves as a receptor and attaches to a protein ligand presented by nearby cells.

The researchers determined that this interaction permits the release of the internal portion of Notch, which travels to the nucleus to influence gene activity so that a cell becomes one of two cell types, such as a neuron or an epidermal cell.

Notch's tail fragment is thought to be released from the cell surface in a process involving a protein that also helps cleave the tail of an Alzheimer's disease-related protein. This protein, amyloid precursor protein (APP), gives rise to a smaller fragment that forms plaques in the brains of patients with the disease.

The study in Molecular Cell reveals that Notch sheds its outer portion when it attaches to other cells. Kopan and his colleagues have given the name NEXT (Notch extracellular truncation) to the remainder.

He postulates that Notch unfurls itself when it binds to ligand, making the outer portion susceptible to cleavage. This cleavage creates NEXT, which Kopan’s study shows is the version of Notch from which the inner tail is released.

Kopan compares unbound Notch to a mousetrap that is ready to spring into action once a mouse steps on the bait. "Notch at the surface is cocked and ready to go," he says. "If a ligand binds to it, a series of proteolytic cleavages releases Notch's business end — the intracellular fragment that goes to the nucleus to create a change (in cell behavior)."

Other investigators in the same issue of Molecular Cell identified the enzyme that cleaves the outer portion of Notch and APP. In combination, the papers' results suggest that Alzheimer researchers should more closely evaluate APP to determine whether it receives signals from nearby cells, Kopan says. In the past two years, scientists have identified five proteins in addition to Notch and APP that undergo cleavage at membranes.

###

Mumm JS, Schroeter EH, Saxena MT, Tian X, Griesemer A, Pan DJ, Ray WJ, Kopan R. Ligand induced "ectodomain shedding" regulates gamma-secretase-like proteolytic activation of Notch1. Molecular Cell, 5 (2): 197-206, Feb. 25, 2000.

A review of protein processing at membranes: Brown MS, Ye J, Rawson RB, Goldstein JL. Regulated Intramembrane Proteolysis: A Control Mechanism Conserved from Bacteria to Humans. Cell ,100 (4): 391-398, Feb. 18, 2000.

This research was funded by a grant from the National Institute of General and Medical Sciences and by a Lucille P. Markey Pathway fellowship.


Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "A Protein-Processing Program Plays A Role In Cell Signaling." ScienceDaily. ScienceDaily, 1 March 2000. <www.sciencedaily.com/releases/2000/03/000301074110.htm>.
Washington University School Of Medicine. (2000, March 1). A Protein-Processing Program Plays A Role In Cell Signaling. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2000/03/000301074110.htm
Washington University School Of Medicine. "A Protein-Processing Program Plays A Role In Cell Signaling." ScienceDaily. www.sciencedaily.com/releases/2000/03/000301074110.htm (accessed July 22, 2014).

Share This




More Plants & Animals News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

San Diego Zoo Welcomes New, Rare Rhino Calf

San Diego Zoo Welcomes New, Rare Rhino Calf

Reuters - US Online Video (July 21, 2014) An endangered black rhino baby is the newest resident at the San Diego Zoo. Sasha Salama reports. Video provided by Reuters
Powered by NewsLook.com
Shark Sightings a Big Catch for Cape Tourism

Shark Sightings a Big Catch for Cape Tourism

AP (July 21, 2014) A rise in shark sightings along the shores of Chatham, Massachusetts is driving a surge of eager vacationers to the beach town looking to catch a glimpse of a great white. (July 21) Video provided by AP
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
A Centuries' Old British Tradition Is Far from a Swan Song

A Centuries' Old British Tradition Is Far from a Swan Song

AFP (July 19, 2014) As if it weren't enough that the Queen is the Sovereign of the UK and 15 other Commonwealth realms, she is also the owner of all Britain's unmarked swans. Duration: 02:18 Video provided by AFP
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:
from the past week

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