Researchers map signaling networks that control neuron function

January 28, 2008
Researchers map signaling networks that control neuron function
Mouse neuron showing multiple neurites with fan-shaped growth cones. Credit: UCSD School of Medicine

In the first large-scale proteomics study of its kind, researchers at the University of California, San Diego School of Medicine have mapped thousands of neuronal proteins to discover how they connect into complex signaling networks that guide neuron function. Their research – using quantitative mass spectrometry, computational software and bioinformatics to match the proteins to their cellular functions – may lead to a better understanding of brain development, neurodegenerative diseases, and spinal cord regeneration.

Led by Richard Klemke, Ph.D., professor of pathology at UCSD School of Medicine and the Moores UCSD Cancer Center, the research team designed a new technology enabling them to, for the first time, isolate and purify neurites – long membrane extensions from the neuron that give rise to axons or dendrites.

This technological breakthrough opens the door to understanding how neurites form and differentiate to regenerate neuronal connections and give rise to a functioning network. It also led to the discovery of how two key signaling molecules are regulated by a complex protein network that controls neurite outgrowth. Their study will be published the week of January 28 to February 1 in the on-line, early edition of the journal Proceedings of the National Academy of Science.

The formation of neurites, a process called neuritogenesis, is the first step in the differentiation of neurons, the basic information cells of the central nervous system.

“Understanding how neurites form is crucial, as these structures give rise to the specialized axons and dendrites which relay sensory input and enable us to see, hear, taste, reason and dream,” said Klemke.

Neurons regenerate by sending out one or several long, thin neurites that will ultimately differentiate into axons, which primarily receive signals, or dendrites, primarily involved in sending out signals. These long, branch-like protrusions have a specialized sensory structure called a growth cone that probes the extracellular environment to find its way and determine which direction the neurite should move in order to hook up with other neurites that will also differentiate into axons and dendrites.

The neural signaling network of dendrites and axons forms a huge information grid, which the UCSD team is studying in order to discover how neurons connect properly and regenerate to maintain proper wiring of the brain. Understanding the role that neuritogenesis plays in the regeneration of nerve connections damaged by diseases such as Alzheimer’s, Parkinson’s or other neurogenerative diseases is an important component of mapping the signaling network.

“Our primary goal is to identify unique proteins that cause the neurite to sprout and differentiate,” said Klemke. “We also want to understand the underlying signals that guide neurite formation and migration in response to directional cues.”

Klemke’s postdoctoral associates Olivier Pertz and Yingchun Wang identified a complex network of enriched proteins called GEFs and GAPs that control neuritogenesis by modulating signaling.

“This signaling provides external guidance cues to mechanical mechanisms inside the cell that make the neurite go forward, turn, or reverse direction,” Klemke said. “Understanding how the thousands of neurite proteins work in concert may someday help us guide neurites to the right place in the body to regenerate and reverse the impact of neural degenerative diseases or help facilitate spinal cord healing after injury.”

The researchers developed a unique microporous filter technology to separate the neurite from the cell body of the neuron, called the soma. The ability to slice millions of neurons into their soma and neurite components opened the door to using mass spectrometry, a tool able to identify the thousands of proteins that uniquely compose the two structures. Using information gleaned from published work, the researchers were then able to predict the function of most of the neurite proteins. This allowed them to construct a blueprint of how the thousands of proteins work together to facilitate neurite formation.

Source: University of California - San Diego

Explore further: Unraveling Alzheimer's: New study documents how brain cells go bad

Related Stories

Unraveling Alzheimer's: New study documents how brain cells go bad

August 29, 2017
In the brains of people with Alzheimer's disease, there are abnormal deposits of amyloid beta protein and tau protein, and swarms of activated immune cells. But scientists do not fully understand how these three major factors ...

Protein associated with Alzheimer's disease linked to cognitive ability

August 14, 2017
If the knowledge that our brains can produce new cells in adulthood is ever going to help in the fight against neurodegenerative disease, we need to understand the underlying mechanisms more effectively. Towards this end, ...

A protein involved in Alzheimer's disease may also be implicated in cognitive abilities in children

August 2, 2017
Rare mutations in the amyloid precursor protein (APP) have previously been shown to be strongly associated with Alzheimer's disease (AD). Common genetic variants in this protein may also be linked to intelligence (IQ) in ...

Researchers help find pathologic hallmarks of Alzheimer's in aged chimpanzee brains

August 1, 2017
Dementia affects one-third of all people older than 65 years in the United States. The most common cause of dementia is Alzheimer's disease, a progressive, irreversible brain disease that results in impaired cognitive functioning ...

A drug-screening platform for ALS

August 2, 2012
A research group at the Center for iPS Cell Research and Application (CiRA) at Japan's Kyoto University has successfully recapitulated amyotrophic lateral sclerosis (ALS)-associated abnormalities in motor neurons differentiated ...

Pair of proteins gets brain cells into shape

December 20, 2012
Scientists at the German Center for Neurodegenerative Diseases in Bonn have gained new insights into the early phase of the brain's development. In cooperation with researchers of the Max Planck Institute of Neurobiology, ...

Recommended for you

Exosomes are the missing link to insulin resistance in diabetes

September 21, 2017
Chronic tissue inflammation resulting from obesity is an underlying cause of insulin resistance and type 2 diabetes. But the mechanism by which this occurs has remained cloaked, until now.

Thousands of new microbial communities identified in human body

September 20, 2017
A new study of the human microbiome—the trillions of microbial organisms that live on and within our bodies—has analyzed thousands of new measurements of microbial communities from the gut, skin, mouth, and vaginal microbiome, ...

Study finds immune system is critical to regeneration

September 20, 2017
The answer to regenerative medicine's most compelling question—why some organisms can regenerate major body parts such as hearts and limbs while others, such as humans, cannot—may lie with the body's innate immune system, ...

Immune cells produce wound healing factor, could lead to new IBD treatment

September 20, 2017
Specific immune cells have the ability to produce a healing factor that can promote wound repair in the intestine, a finding that could lead to new, potential therapeutic treatments for inflammatory bowel disease (IBD), according ...

As men's weight rises, sperm health may fall

September 20, 2017
(HealthDay)—A widening waistline may make for shrinking numbers of sperm, new research suggests.

New model may help science overcome the brain's fortress-like barrier

September 19, 2017
Scientists have helped provide a way to better understand how to enable drugs to enter the brain and how cancer cells make it past the blood brain barrier.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

zevkirsh
not rated yet Jan 29, 2008
neuron research is the consistently the most eye-popping area where i find that obvious new areas for questioning are being ideentitfied and explored on a yearly basis. what's next!?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.