Navigation Links
Hopkins researchers put proteins right where they want them
Date:4/14/2010

Using a method they developed to watch moment to moment as they move a molecule to precise sites inside live human cells, Johns Hopkins scientists are closer to understanding why and how a protein at one location may signal division and growth, and the same protein at another location, death.

Their research, published Feb. 14 in Nature Methods, expands on a more limited method using a chemical tool to move proteins inside of cells to the periphery, a locale known as the plasma membrane.

"Where a particular protein is activated and the timing of that activation influence how a cell responds to outside stimulus," says Takanari Inoue, Ph.D., an assistant professor of cell biology at Johns Hopkins University School of Medicine. "Our goal with this newly expanded tool is to manipulate protein activities in many places in cells on a rapid timescale."

Cells cleverly have resolved the predicament of needing to respond to a near infinite array of external stimuli temperature, for instance even though they employ only a limited number of molecular players. The notion is that a single protein assumes multiple roles by changing its location or altering the speed and duration of activation.

Chemical signaling inside cells connects protein molecules through complex feedback loops and crosstalk, Inoue says, so knowing exactly how each protein contributes to which signals at what locations requires the ability to rapidly move proteins of interest to specific organelles found in cells. These include mitochondria (the power generators of cells) and Golgi bodies (the delivery systems of cells).

The Hopkins team chose the signaling protein Ras as the molecule it would attempt to send packing throughout a cell's interior. A regulator of cell growth that's often implicated in cancer, Ras has been long studied and it's known to be a molecular switch. However, no one has had the ability to discern what Ras does at different locations such as Golgi bodies and mitrochondria, much less what happens when Ras is activated simultaneously at any combination of these and other organelles.

Working with live human HeLa cells and Ras under a microscope, the team used a dimerization probe consisting of a special small molecule that simultaneously attracts two proteins that wouldn't normally have an affinity for each other and binds them together. In this system, one of the partner proteins is anchored to an organelle and the other is free floating inside the cell. Adding a chemical dimerizer induces the free protein to join the tethered one.

Using scissor-like enzymes, the team sliced and diced the DNA of the paired proteins to change the molecular address of its destination. They cut out the "mailing address" known as a targeting sequence that formerly delivered the protein unit to the plasma membrane and replaced it with new addresses (targeting sequences) that shipped it instead to specific organelles.

"We were able to manipulate protein activities in situ and very rapidly on each individual organelle," Inoue said. "Ultimately, this will help us to better understand protein function at these critical cellular components."


'/>"/>

Contact: Maryalice Yakutchik
myakutc1@jhmi.edu
443-287-2251
Johns Hopkins Medical Institutions
Source:Eurekalert  

Related biology news :

1. Pancreatic Cancer Action Network-AACR Pathway to Leadership Grant awarded to Johns Hopkins Early Career investigator
2. Johns Hopkins scientists discover a controller of brain circuitry
3. Hopkins scientists ID 10 genes associated with a risk factor for sudden cardiac death
4. Johns Hopkins scientists pull proteins tail to curtail cancer
5. Johns Hopkins researchers detect sweet cacophony while listening to cellular cross-talk
6. Hopkins researchers piece together gene network linked to schizophrenia
7. Johns Hopkins scientists discover what drives the development of a fatal form of malaria
8. Worth a thousand words: Hopkins researchers paint picture of cancer-promoting culprit
9. Vaginal reconstruction not needed for most inter-sex females, Hopkins study shows
10. EVMS researchers identify potential target for treatment of obesity-related diseases
11. UI researchers analyze implications of intelligent design for human behavior
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Hopkins researchers put proteins right where they want them
(Date:5/3/2016)... , May 3, 2016  Neurotechnology, a ... the MegaMatcher Automated Biometric Identification System (ABIS) ... large-scale multi-biometric projects. MegaMatcher ABIS can process multiple ... using any combination of fingerprint, face or iris ... MegaMatcher SDK and MegaMatcher Accelerator , ...
(Date:4/28/2016)... 2016 First quarter 2016:   ... with the first quarter of 2015 The gross margin ... (loss: 18.8) and the operating margin was 40% (-13) ... Cash flow from operations was SEK 249.9 M (21.2) , ... unchanged, SEK 7,000-8,500 M. The operating margin for 2016 ...
(Date:4/26/2016)... 27, 2016 Research and ... Biometrics Market 2016-2020"  report to their offering.  , ... The analysts forecast the global multimodal biometrics ... during the period 2016-2020.  Multimodal biometrics ... such as the healthcare, BFSI, transportation, automotive, and ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... 27, 2016  Global demand for enzymes is ... 2020 to $7.2 billion.  This market includes enzymes ... products, biofuel production, animal feed, and other markets) ... biocatalysts). Food and beverages will remain the largest ... consumption of products containing enzymes in developing regions.  ...
(Date:6/27/2016)... ... June 27, 2016 , ... Cancer experts from ... believe could be a new and helpful biomarker for malignant pleural mesothelioma. Surviving ... to read it now. , Biomarkers are components in the blood, tissue ...
(Date:6/27/2016)... ... June 27, 2016 , ... ... will join the faculty of the University of North Carolina Kenan-Flagler Business ... strategy and entrepreneurship at UNC Kenan-Flagler, with a focus on the school’s international ...
(Date:6/24/2016)... 24, 2016  Regular discussions on a range of subjects ... the two entities said Poloz. Speaking at a ... , he pointed to the country,s inflation target, which ... "In certain areas ... have common economic goals, why not sit down and address ...
Breaking Biology Technology: