Dendrites - How The Neuron Sprouts Its Branches

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Dendrites - How The Neuron Sprouts Its Branches

http://www.medicalnewstoday.com/medicalnews.php?newsid=34758

Neurobiologists have gained new insights into how neurons control

growth of the intricate tracery of branches called dendrites that

enable them to connect with their neighbors. Dendritic connections

are the basic receiving stations by which neurons form the signaling

networks that constitute the brain's circuitry.

Such basic insights into neuronal growth will help researchers better

understand brain development in children, as well as aid efforts to

restore neuronal connections lost to injury, stroke or

neurodegenerative disease, said the researchers.

In a paper published in the Dec. 8, 2005, issue of Neuron,

Medical Institute investigator Ehlers and his

colleagues reported that structures called " Golgi outposts " play a

central role as distribution points for proteins that form the

building blocks of the growing dendrites.

Besides Ehlers, who is at Duke University Medical Center, other co-

authors were April Horton in Ehlers' laboratory; Weinberg of

the University of North Carolina at Chapel Hill.; Bence Rácz in

Weinberg's laboratory; and Monson and Lin of Duke's

Department of Physics. The research was sponsored by The National

Institutes of Health.

The Golgi apparatus is a cellular warehouse responsible for

receiving, sorting and shipping cargoes of newly synthesized

molecules needed for cell growth and function. Until the new

findings, researchers believed that only a central Golgi apparatus

played a role in such distribution, said Ehlers.

" In most mammalian cells, the Golgi has a very stereotyped structure,

a stacked system that resides near the cell nucleus in the middle of

the cell, " he said. " But mammalian neurons in the brain are huge,

with a surface area about ten thousand times that of the average

cell. So, it was an entirely open question where all the membrane

components came from to generate the complex surface of growing

dendrites. And we thought these remote structures we had discovered

in dendrites called Golgi outposts might play a role. "

The researchers studied the dendritic growth process in pyramidal

neurons, which grow a single long " apical " dendrite and many shorter

ones. To explore the role of Golgi outposts, they used imaging of

living rat brain cells grown in culture, as well as electron

microscopy of rat brain tissue.

These studies revealed that the Golgi outposts tended to appear in

longer dendrites and also that those Golgi in the main cell body

tended to orient toward longer dendrites. And importantly, said

Ehlers, the studies in cell culture revealed that the Golgi

orientation preceded the preferential growth of long dendrites.

" This finding showed us that we weren't just seeing a correlation

between Golgi and longer dendrites, " said Ehlers. " Initially, when

these growing dendrites are all essentially uniform in length, they

grow at about the same rate. But later, after the Golgi orient toward

one dendrite, it takes off and grows dynamically to become the

longest dendrite. " The researchers also used tracer molecules to

track the molecular cargo secreted by the Golgi, said Ehlers.

" We saw very clearly that this cargo that originates in the Golgi

gets directed towards the one longest dendrite in a highly

preferential way, " he said. " As cargo comes out of the Golgi, it does

not go randomly to the cell surface. " Ehlers and his colleagues also

found that the Golgi outposts appeared to locate themselves at

dendritic branch points.

" This finding is important because a fundamental problem that neurons

must solve is how to sort appropriate cargo molecules in the right

amounts down different dendritic branches, " said Ehlers. " After all,

different dendritic branches can have different functional

properties, molecular composition and electrical properties. So, when

a cargo reaches a branch point, it's like a highway intersection, and

the cargo needs to be directed. We've found that these dendritic

Golgi outposts are located at the strategic points to do just that.

And I believe this is the first such specific organelle identified at

a dendritic branch point positioned to perform this fundamental

neuronal function. "

Finally, the researchers disrupted the orientation, or " polarity, " of

the Golgi -- thus causing them to move into all the dendrites --

without disrupting their function. They found that disrupting the

polarity caused all the dendrites to grow at the same rate.

Further studies, said Ehlers, will explore how Golgi outposts arise,

how they arrive at dendritic branch points and what cargo they

distribute. The researchers also will seek to understand how

molecules are selected for import to the distant reaches of the

dendrites and which will be locally synthesized in the dendrites.

Such studies could give important insights into the machinery of

neuronal growth and how it is controlled, he said.

" Understanding this machinery has clinical relevance because many

disorders of brain development in children manifest abnormal

dendritic structures, " said Ehlers. " Also, it turns out that most

neurodegenerative diseases, such as Parkinson's and Alzheimer's, are

disorders of protein processing. But we know very little about how

and where integral membrane proteins are synthesized and processed by

neurons. "

Duke University Medical Center

http://www.dukemednews.org