Skip Ribbon Commands
Skip to main content
Translate
Donations
menu iconMenu
search iconSearch

Researchers Map Signaling Networks that Control Neuron Function

 

January 28, 2008  |  

Relationship between Thousands of Proteins at Work in the Brain Could Impact Diseases such as Alzheimer’s, Parkinson’s Disease, and Spinal Cord Injury

In the first large-scale proteomics study of its kind, researchers at the University of California, San Diego (UCSD) 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.

Neurite

Mouse neuron showing multiple neurites with fan-shaped growth cones.  Click Here to see video.

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. 

Contributors to the study include Richard D. Smith, Feng Yang, and David G. Camp II, Biological Sciences Division, Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA; and Olivier C. Pertz, Yingchun Wang, Wei Wang, Laurie J. Gay, UCSD Department of Pathology and Moores UCSD Cancer Center.

The work was funded by grants from the National Institutes of Health, the Susan G. Komen Foundation, and a Cell Migration Consortium Grant.  The Environmental Molecular Sciences Laboratory is a U.S. Department of Energy national scientific user facility.

# #  #

Media Contact: Debra Kain, 619-543-6163, ddkain@ucsd.edu


Related Specialties

UCSD Moores Cancer Center


Media Contact

Related News

5/21/2015
Using human embryonic stem cells, researchers at University of California, San Diego School of Medicine and Moores Cancer Center and Sanford-Burnham Medical Research Institute created a model that all ...
5/18/2015
A binational team from the University of California, San Diego School of Medicine and the U.S.-Mexico Border Health Commission, Mexico Section has launched a new research project aimed at promoting pr ...
5/17/2015
For parents who send their kids to dance classes to get some exercise, a new study from researchers at University of California, San Diego School of Medicine suggests most youth dance classes provide ...
5/8/2015
Therapies that specifically target mutations in a person’s cancer have been much-heralded in recent years, yet cancer cells often find a way around them. To address this, researchers at University of ...
5/7/2015
Researchers at University of California, San Diego School of Medicine and Shiley Eye Institute have identified the molecular “glue” that builds the brain connections that keep visual images clear and ...
5/7/2015
Writing in the May 7 online issue of American Journal of Geriatric Psychiatry, researchers at University of California, San Diego School of Medicine and Veterans Affairs San Diego Healthcare System su ...
5/6/2015
Each year, more than 10 million Americans seek medical attention, often in emergency situations, for symptoms of intestinal blockages. Researchers at the University California, San Diego School of Med ...
5/6/2015
With the threat of multidrug-resistant bacterial pathogens growing, new ideas to treat infections are sorely needed. Researchers at University of California, San Diego School of Medicine and Skaggs Sc ...


Share This Article



Follow Us