Motor Protein Plays Key Role In Connecting Neurons

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Motor Protein Plays Key Role In Connecting Neurons

http://www.sciencedaily.com/releases/2007/01/070122182947.htm

A motor protein called myosin X runs the main road of a developing

neuron, delivering to its tip a receptor that enables it to

communicate with other neurons, scientists say.

Dr. Wen-Cheng Xiong, developmental neurobiologist at the Medical

College of Georgia. (Phil photo)NaNIn another piece of the

puzzle of how neurons form connections, researchers have found

myosin X travels a portion of a neuron's backbone called the actin

filament, a sort of two-way highway in the cell's highest traffic

area, says Dr. Wen-Cheng Xiong, developmental neurobiologist at the

Medical College of Georgia.

Part of its cargo is DCC receptor which needs to move from the

central nucleus where it's synthesized to the cell's periphery, Dr.

Xiong and her colleagues report in the February issue of Nature Cell

Biology and available online Jan. 21.

At the periphery, DCC interacts with netrin-1, a guidance cue for

helping the arm-like extension of the cell, called the axon, grow in

the right direction. Cells eventually communicate through synapses

at the end of these cellular projections.

" During early development, axons need to grow, they need to find a

target, they need to decide how long to grow, which direction to

grow. Eventually they will form a synapse, " says Dr. Xiong, who is

dissecting how neurons first connect with the goal of helping

restore communication lost in spinal cord injuries and other

disorders.

" Growth is precisely controlled during development, " she says and

errant growth can impair brain wiring or connectivity. " Myosin X

gets the DCC receptor where it needs to be so it can interact with

netrin-1. "

Her previous studies, published in 2004 in Nature Neuroscience,

showed that DCC binding to netrin-1, activates an enzyme, focal

adhesion kinase, enabling developing cells to reorganize and

intuitively know how to move. The process enables brain cells to

reach out to each other and across the midline of the developing

brain and spinal cord. When the kinase is deleted, the axon doesn't

make the proper connections.

When researchers cut off myosin X's motor -- which they believe

happens in spinal cord injuries -- axon outgrowth also was hindered.

" Myosin X plays a critical role in neurons during development, " says

Dr. Xiong. Different versions of the myosin family proteins are

critical to essentially every cell including muscle cells and those

that turnover and divide rapidly, such as skin and intestinal cells,

and eggs or oocytes.

The rapidly moving protein is easily degraded and needs tight

regulation. " If you don't want to have dramatic changes in your

neuron structure, you don't want this molecule, " she says.

In fact, she suspects the function of myosin X changes as the neuron

develops. She has documented that in late stages of development,

when the axon needs to stop growing, a shorter molecule, minus the

motor, is expressed. " Probably after the neuron is developed, the

major work of myosin is done. There are many cleavage sites in the

middle and this typically large molecule can be cut down to a small

molecule that actually inhibits axon growth function, " Dr. Xiong

says.

She suspects that negative function surfaces when the spinal cord is

cut and plans to examine whether the protein is degraded in spinal

cord injuries. " We already have evidence that if this protein

degrades, most frequently without its motor domain, it becomes

negative, inhibits DCC getting to the proper place and so axonal

growth, " Dr. Xiong says.

The work was funded by the National Institutes of Health. Co-authors

include Dr. Xiao- Zhu, former postdoctoral fellow in Dr. Xiong's

lab, Dr. PengGao Dai, former postdoctoral fellow in Dr. Lin Mei's

laboratory at MCG and Dr. Yu-Qiang Ding's laboratory at the

Institute of Neuroscience and Key Laboratory of Neurobiology,

Shanghai Institutes for Biological Sciences, Chinese Academy of

Sciences.

Note: This story has been adapted from a news release issued by

Medical College of Georgia.