Corporate Banner
Satellite Banner
Proteomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Key Protein is Linked to Circadian Clocks, Helps Regulate Metabolism

Published: Wednesday, June 19, 2013
Last Updated: Wednesday, June 19, 2013
Bookmark and Share
Study sheds light on molecular basis for metabolic health and disease.

Inside each of us is our own internal timing device. It drives everything from sleep cycles to metabolism, but the inner workings of this so-called “circadian clock” are complex, and the molecular processes behind it have long eluded scientists.

But now, researchers at the Gladstone Institutes have discovered how one important protein falls under direct instructions from the body’s circadian clock. Furthermore, they uncover how this protein regulates fundamental circadian processes – and how disrupting its normal function can throw this critical system out of sync.

In the latest issue of the Journal of Neuroscience, Gladstone investigator Katerina Akassoglou, PhD, and her team reveal in animal models how the production of the p75 neurotrophin receptor (p75NTR) protein oscillates in time with the body’s natural circadian clock – and how these rhythmic oscillations help regulate vital metabolic functions. This discovery underscores the widespread importance of p75NTR by offering insight into how the circadian clock helps maintain the body’s overall metabolic health.

Virtually every organism on the planet – from bacteria to humans – has a circadian clock, a biological timing mechanism that oscillates with a period of about 24 hours and is coordinated with the cycle of day and night.

While it runs independent of external cues, it is influenced by the rhythms of light, temperature and food availability. Intriguingly, recent studies have also found a link between circadian clocks and metabolism.

“Important metabolic functions are also heavily influenced by circadian clocks, which is why activities such as chronic night-shift work – which can cause a misalignment of this clock – increase one’s risk for metabolic and autoimmune diseases such as obesity, Type 2 diabetes, cancer and multiple sclerosis,” said Akassoglou, who is also a professor of neurology at UC San Francisco, with which Gladstone is affiliated. “In this study, we pinpointed p75NTR as an important molecular ‘link’ between circadian clocks and metabolic health.”

Key Protein Found Throughout the Body

Originally, p75NTR was only thought to be active in the nervous system. Later studies found it to be active in many cell types throughout the body, suggesting that it impacts a variety of biological functions.

Last year, Gladstone researchers discovered that p75NTR was present in the liver and in fat cells, and that it regulates glucose levels in the blood – an important metabolic process. Since these findings uncovered a link between p75NTR and metabolism, the research team tested – first in a petri dish and then in animal models – whether there was also a link between p75NTR and the circadian clock.

The team focused on two genes called Clock and Bmal1. These so-called “circadian regulator genes,” and others like them, are found throughout the body. Their activity controls the body’s circadian clock. The researchers wanted to see if there was a connection between these circadian genes and p75NTR.

“Our initial experiments revealed such a connection,” recalls Gladstone postdoctoral fellow Bernat Baeza-Raja, PhD, the paper’s lead author. “In individual cells, we saw that p75NTR production was controlled by Clock and Bmal1, which bind directly to the gene that codes for the p75NTR and start production of the protein.”

P75NTR’s Impact on Circadian Clock Systems

But perhaps even more important than how p75NTR was produced was when. The team found that p75NTR production, like the circadian clock genes themselves, oscillated in a 24-hour cycle – in sync with the cells’ natural circadian rhythm. Experiments in mouse models further supported these findings.

And when the team genetically modified a group of mice so that it lacked the circadian Clock gene, everything else fell out of sync. The circadian oscillation of p75NTR production was disrupted, and p75NTR levels dropped.

However, what was most fascinating, say the researchers, was how a drop in p75NTR levels then affected a variety of circadian clock systems. Specifically, the regular oscillations of other circadian genes in the brain and the liver became disrupted, as well as genes known to regulate glucose and lipid metabolism.

“The finding that a loss of p75NTR affected circadian and metabolic systems is strong evidence that this protein is intricately tied to both,” said Life Sciences Institute director Alan Saltiel, PhD, who is also a professor at the University of Michigan and was not involved in the study. “It will be fascinating to see what additional insight Dr. Akassoglou and her team will uncover as they continue to examine the role of p75NTR in circadian clocks and metabolic function.”

“While these findings reveal p75NTR to be an important link between circadian clocks and metabolism, the system is complex, and there are likely other factors at play,” said Akassoglou. “We are currently working to identify the relationship between the circadian clock, metabolism and the immune system, so that one day we could develop therapies to treat diseases influenced by circadian clock disruption – including not only obesity and diabetes, but also potentially multiple sclerosis and even Alzheimer’s disease.”


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Industry-Sponsored Academic Inventions Spur Increased Innovation
Analysis questions assumption that corporate support skews science toward inventions that are less useful than those funded by the government or non-profit organizations.
Monday, March 24, 2014
Structure of Key Pain-Related Protein Unveiled
In a technical tour de force, scientists have determined, at near-atomic resolution, the structure of a protein that plays a central role in the perception of pain and heat.
Friday, December 06, 2013
Chemical Signature for Fast Form of Parkinson's Found
The physical decline experienced by Parkinson's disease patients eventually leads to disability and a lower quality of life.
Monday, November 25, 2013
New Insights into How Proteins Regulate Genes
Researchers have developed a new way to parse and understand how special proteins called "master regulators" read the genome, and consequently turn genes on and off.
Monday, October 21, 2013
Cell Growth Discovery Has Implications for Targeting Cancer
The way cells divide to form new cells is controlled in previously unsuspected ways.
Monday, October 21, 2013
Discovery Could Lead to Saliva Test for Pancreatic Cancer
The disease is typically diagnosed through an invasive and complicated biopsy.
Tuesday, October 15, 2013
Tuberculosis and Parkinson’s Disease Linked by Unique Protein
UCSF researchers seek way to boost protein to fight both diseases.
Wednesday, September 11, 2013
Effects of Parkinson’s Disease Mutation Reversed in Cells
UCSF study used chemical commonly found in anti-wrinkle cream.
Friday, August 23, 2013
Dentistry School Receives $5M to Study Saliva Biomarkers
Imagine having a sample of your saliva taken at the dentist's office, and then learning within minutes whether your risk for stomach cancer is higher than normal.
Thursday, August 15, 2013
Scientists Devise Innovative Method to Profile and Predict the Behavior of Proteins
A class of proteins that are made up of multiple, interlocking molecular components, enzymes perform a variety of tasks inside each cell.
Friday, August 09, 2013
Immune System Molecule Promotes Tumor Resistance
A team of scientists has shown for the first time that a signaling protein involved in inflammation also promotes tumor resistance to anti-angiogenic therapy.
Tuesday, August 06, 2013
Failure to Destroy Toxic Protein Contributes to Progression of Huntington’s Disease
Gladstone-led study also finds target that boosts protein clearance, prolongs cell life.
Tuesday, July 23, 2013
Deadliest Cancers May Respond to New Drug Treatment Strategy
Researchers have found a way to knock down cancers caused by a tumor-driving protein called “myc,” paving the way for clinical trials.
Monday, July 22, 2013
Brain Anomolies are Potential Biomarkers for Autism
Brain anomalies may serve as potential biomarkers for the early identification of the neurodevelopmental disorder.
Wednesday, July 10, 2013
Second Amyloid May Play a Role in Alzheimer's
The study is the first to identify deposits of the protein, called amylin, in the brains of people with Alzheimer's disease.
Monday, July 01, 2013
Scientific News
Lemon Juice and Human Norovirus
Citric acid may prevent the highly contagious norovirus from infecting humans, scientists discovered from the German Cancer Research Center.
Signature of Microbiomes Linked to Schizophrenia
Studying microbiomes in throat may help identify causes and treatments of brain disorder.
Structural Discoveries Could Aid in Better Drug Design
Scientists have uncovered the structural details of how some proteins interact to turn two different signals into a single integrated output.
Protein Found to Play a Key Role in Blocking Pathogen Survival
Calprotectin fends off microbial invaders by limiting access to iron, an important nutrient.
Study Identifies the Off Switch for Biofilm Formation
New discovery could help prevent the formation of infectious bacterial films on hospital equipment.
How DNA ‘Proofreader’ Proteins Pick and Edit Their Reading Material
Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have discovered how two important proofreader proteins know where to look for errors during DNA replication and how they work together to signal the body’s repair mechanism.
Protein Found to Control Inflammatory Response
A new Northwestern Medicine study shows that a protein called POP1 prevents severe inflammation and, potentially, diseases caused by excessive inflammatory responses.
X-ray Laser Experiment Could Help in Designing Drugs for Brain Disorders
Scientists found that when two protein structures in the brain join up, they act as an amplifier for a slight increase in calcium concentration, triggering a gunshot-like release of neurotransmitters from one neuron to another.
Team Identifies Structure of Tumor-Suppressing Protein
An international group of researchers led by Carnegie Mellon University physicists Mathias Lösche and Frank Heinrich have established the structure of an important tumor suppressing protein, PTEN.
Why We’re Smarter Than Chickens
Toronto researchers have discovered that a single molecular event in our cells could hold the key to how we evolved to become the smartest animal on the planet.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!