Contrary to belief, crucial protein for peripheral nerve repair is manufactured within the axon near the injury site

July 25, 2012

Several years ago, Prof. Michael Fainzilber and his group in the Biological Chemistry Department made a surprising discovery: Proteins thought to exist only near the cell nucleus could also be found in the far-off regions of the body's longest cells – peripheral nerve cells that extend processes called axons, reaching up to a meter in length in adult humans.

These proteins, known as importins, have a well-studied role in the vicinity of the nucleus: They shuttle various molecules through the protective nuclear membrane. Fainzilber and his group showed that when a nerve cell is injured somewhere along its length, importins in the long axons hook into a sort of "railcar" mechanism, which then transports the "Help!" message from the injury site all the way to the nucleus.

These findings raised an intriguing question: How did importins get to the axons in the first place? Initial evidence suggested that one critical importin, called importin beta1, is produced locally upon injury near the site where it is needed. The problem was that years of scientific thinking on the subject indicated that proteins do not get manufactured in the axons, as investigations had turned up few of the cellular protein factories known as ribosomes there.

Settling the issue was far from simple: Importins are so crucial that even the smallest embryo could not survive without them. But Rotem Ben-Tov Perry, a joint research student in Fainzilber's group and that of department colleague Dr. Avraham Yaron, found a way to distinguish the importin beta1 in the cell body from that in the axon: The axonal protein was apparently made from a longer messenger RNA. To see if they could selectively affect just the axonal version of the protein, the groups, together with Prof. Jeff Twiss of Drexel University, Philadelphia, Pennsylvania, took advantage of high precision knock-out technology. Rather than knocking a whole gene out of the system, they managed to remove one little piece of the messenger RNA that carries the encoded instructions for manufacturing importins: just the longer bit that sends the RNA to the axon.

Now they observed plenty of importin beta1 in the cell body, but none in the axons. Mice with the knocked out segment of RNA took much longer to recover from injury, and the genes that are normally active in response to nerve damage were activated to a lesser degree. All of this suggests that the importin beta1 that normally helps inform the extended nerve cell about injury is, indeed, produced locally in the axon.

Fainzilber: "The data shows conclusively that importin beta1 is produced in , and Rotem's work has validated the importins' crucial role in nerve repair." The findings, which appeared recently in Neuron, may help point the way toward better treatments for nerve damage and aid in finding ways to speed up the repair.

Explore further: Researchers identify protein required to regrow injured nerves in limbs

Related Stories

Researchers identify protein required to regrow injured nerves in limbs

June 20, 2012
A protein required to regrow injured peripheral nerves has been identified by researchers at Washington University School of Medicine in St. Louis.

Stress pathway identified as potential therapeutic target to prevent vision loss

February 8, 2012
A new study identifies specific cell-stress signaling pathways that link injury of the optic nerve with irreversible vision loss. The research, published by Cell Press in the February 9 issue of the journal Neuron, may lead ...

New procedure repairs severed nerves in minutes, restoring limb use in days or weeks

February 3, 2012
American scientists believe a new procedure to repair severed nerves could result in patients recovering in days or weeks, rather than months or years. The team used a cellular mechanism similar to that used by many invertebrates ...

Nerve pathway for combating axon injury and stress may hold benefits for individuals with neurodegenerative disorders

June 27, 2012
(Medical Xpress) -- Researchers from the Huck Institutes' Center for Cellular Dynamics — led by Center director Melissa Rolls — have found that a neuroprotective pathway initiated in response to injured or stressed ...

Recommended for you

Team constructs whole-brain map of electrical connections key to forming memories

November 22, 2017
A team of neuroscientists at the University of Pennsylvania has constructed the first whole-brain map of electrical connectivity in the brain based on data from nearly 300 neurosurgical patients with electrodes implanted ...

To forget or to remember? Memory depends on subtle brain signals, scientists find

November 22, 2017
The fragrance of hot pumpkin pie can bring back pleasant memories of holidays past, while the scent of an antiseptic hospital room may cause a shudder. The power of odors to activate memories both pleasing and aversive exists ...

New research suggests high-intensity exercise boosts memory

November 22, 2017
The health advantages of high-intensity exercise are widely known but new research from McMaster University points to another major benefit: better memory.

Pitch imperfect? How the brain decodes pitch may improve cochlear implants

November 22, 2017
Picture yourself with a friend in a crowded restaurant. The din of other diners, the clattering of dishes, the muffled notes of background music, the voice of your friend, not to mention your own – all compete for your ...

What if consciousness is not what drives the human mind?

November 22, 2017
Everyone knows what it feels like to have consciousness: it's that self-evident sense of personal awareness, which gives us a feeling of ownership and control over the thoughts, emotions and experiences that we have every ...

Now you like it, now you don't: Brain stimulation can change how much we enjoy and value music

November 20, 2017
Enjoyment of music is considered a subjective experience; what one person finds gratifying, another may find irritating. Music theorists have long emphasized that although musical taste is relative, our enjoyment of music, ...

0 comments

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.