How Nerve Cells Stay In Shape

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How Nerve Cells Stay In Shape

http://www.medicalnewstoday.com/medicalnews.php?newsid=36306

Nerve cells store and transmit information via special contact sites

called synapses. Synapses also play a role in determining what we

remember and what we forget. When we learn, both the structure and

the functional characteristics of these contact sites change.

Scientists are only now beginning to understand the molecular

processes which cause that change. Researchers led by Kiebler

at the Max Planck Institute for Developmental Biology in Tübingen

(now at the Center for Brain Research, University of Vienna) have

identified a protein that is essential for the maintenance of

synapses: if the protein Staufen2 is removed in a nerve cell, the

cell loses a large portion of its synapses. Moreover, signalling at

the remaining contact sites is significantly impaired. Staufen

proteins are involved in the transport of molecular blueprints

(mRNAs) to specific locations in a cell. The disturbance in the

structure and function of synapses without Staufen2 protein suggests

that mRNA transport to synapses is crucial to their maintenance and

the storage of memory (Journal of Cell Biology, January 17, 2006).

Nerve cells receive signals from other nerve cells via dendrites,

which branch out like the branches of a tree. The cell-body receives

incoming information, and transmits it further through the axon, a

long projection from the cell. Nerve cells make contact with each

other at highly-specialised locations known as synapses. There,

information is not only passively transmitted. Synapses can,

depending on input, change and in this way store new memory.

A synapse has two parts: one originates from the axon of the sending

cell, the other, from a dendrite of the receiving cell (see image 1).

Both parts comprise a special set of molecules, which clearly

distinguishes them from the rest of the cell. Furthermore, these

contact sites can change structure and characteristics with incoming

signals. In dendrites, these changes can only happen when certain

proteins are produced at the synapse. A prerequisite for protein

synthesis, however, is that the mRNAs carrying the " blueprint " of the

protein actually arrive at the synapse. The mRNAs have to be

recognized by special RNA-binding proteins and transported to the

synapses, which in some cases are a considerable distance from the

cell body. Staufen2 protein is involved in this transport process.

Bernhard Goetze and Paolo Macchi have, for the first time, shown that

the protein Staufen2 is required to maintain synapses. The

researchers knocked-down different proteins in the nerve cells. If

the brain-specific Staufen2 protein was missing, the architecture of

the synapses was severely disturbed. Instead of a number of mushroom-

shaped dendritic spines, the cell only produced long, thin

protuberances (see image 2), similar in shape to immature synapses. A

more detailed analysis of the actin cytoskeleton offered the first

evidence for a possible explanation for the observed synapse changes.

Actin is a central protein in the cell's skeleton, which keeps

synapses in shape. Formless synapses in Staufen2-deficient nerve

cells have significantly fewer actin fibres than normal synapses. The

mRNA for actin is normally transported into dendrites and locally

translated into protein there. If there is no Staufen2 to function as

a transport protein in the nerve cells, a lesser amount of mRNA makes

it to the synapse - this could explain its altered shape.

" We wanted to know if Staufen2-deficient nerve cells can still

transmit signals, " explains Kiebler. In order to determine

this, researchers collaborated with Stefan Boehm's group at the

Medical University of Vienna's Institute of Pharmacology.

Measurements of electrical activity at individual synapses showed

impaired signal transmission in cells lacking Staufen2 protein. " This

was important evidence that Staufen2 is necessary for the formation

of functional synapses in nerve cells, " Kiebler says. His group thus

creates the first conceptual link between molecular processes in the

receiving part of the nerve cell and changes in the structure and

function of its synapses. This could lead to a better understanding

of molecular mechanisms, which lie at the heart of the brain's

ability to learn and to remember.

Original work:

Goetze B, Tuebing F, Xie Y, Dorostkar MM, S, Pehl U, Boehm S,

Macchi P, and Kiebler MA

The brain-specific double-stranded RNA binding protein Staufen2 is

required for dendritic spine morphogenesis.

Journal of Cell Biology, Vol. 172 (2), 17 January 2006