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Subject: FROM NERVE ROOTS TO PLANT ROOTS - RESEARCHERS ARE GAINING
UNEXPECTED INSIGHTS INTO HEREDITARY SPASTIC PARAPLEGIA
U.S. Department of Health and Human Services NATIONAL INSTITUTES OF HEALTH
NIH News National Institute of Neurological Disorders and Stroke (NINDS)
<http://www.ninds.nih.gov/> Embargoed for Release: Thursday, August 6, 2009,
Noon, EDT
CONTACT: Daniel Stimson, NINDS, 301-496-5751 <e-mail:
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FROM NERVE ROOTS TO PLANT ROOTS - RESEARCHERS ARE GAINING UNEXPECTED
INSIGHTS INTO HEREDITARY SPASTIC PARAPLEGIA
Sprouting. Branching. Pruning. Neuroscientists have borrowed heavily from
botanists to describe the way that neurons grow, but analogies between the
growth of neurons and plants may be more than superficial. A new study from
the National Institutes of Health and Harvard Medical School suggests that
neurons and plant root cells may grow using a similar mechanism.
The research also sheds light on the hereditary spastic paraplegias (HSP), a
group of inherited neurological disorders in which some of the longest
neurons in the body fail to grow and function properly. The genes behind HSP
and their roles inside neurons are poorly understood. However, the study
suggests that several forms of HSP share an underlying defect with each
other - and with abnormal root hair development in a plant widely used for
agricultural research.
The strange implication is that the plant, Arabidopsis thaliana (mouse-ear
cress), could prove useful for further research on HSP.
"This study provides us with valuable new insights that will stimulate
research toward therapies for hereditary spastic paraplegias," says Craig
Blackstone, M.D., Ph.D., an investigator at NIH's National Institute of
Neurological Disorders and Stroke (NINDS) and an HSP expert. Dr. Blackstone
performed the study in collaboration with William Prinz, Ph.D., an
investigator at the NIH's National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK), and Tom Rapoport, Ph.D., a Howard Hughes Medical
Institute investigator and a professor of cell biology at Harvard Medical
School.
HSP primarily affects corticospinal neurons, which extend projections called
axons from the brain's cerebral cortex to the spinal cord. The longest
corticospinal axons extend nearly all the way down the spinal cord - a
distance up to about three feet - in order to control movement in the legs.
In HSP, these long axons develop abnormally or they degenerate later in
life, causing muscle stiffness and weakness in the legs. HSP exists in many
forms in different families, and more than 40 genes have been implicated in
the disease.
In the new study, published in Cell, the researchers propose that defects in
the shaping of a subcellular structure known as the endoplasmic reticulum
(ER) are a common cause of HSP. The ER - named for its reticulated (or
net-like) shape - is a cellular factory, where molecules such as proteins
and lipids that are vital to cell growth are made and packaged for shipping
to various cellular destinations. The researchers theorize that in several
forms of HSP, the ER loses its complex shape and is unable to support the
growth or maintenance of long corticospinal axons.
Several years ago, other researchers showed that similar ER defects in
Arabidopsis impair the growth of the plant's root hairs. These are wispy,
microscopic projections that grow from the plant's individual root cells.
The new study focuses on a gene called atlastin. This gene is defective in
about 10 percent of HSP cases, and in previous research, Dr. Blackstone's
group showed that it has a role in axon growth. The new study reveals that
the atlastin protein is necessary for maintaining the shape of the ER in
mammalian cells, and that an analogous protein called Sey1p performs the
same function in baker's yeast.
The researchers demonstrate that ER shaping defects have general relevance
for HSP, by showing a connection between atlastin and a group of proteins
known as the DP1 family. Years ago, Drs. Prinz and Rapoport reported that a
yeast analog of DP1 regulates the shape of the ER in yeast. Meanwhile,
others researchers had independently reported that mutations in REEP1, a
member of the DP1 family, cause 3 percent to 8 percent of HSP cases. The new
study shows that atlastin interacts physically with DP1 in mammalian cells,
and that Sey1p (the yeast atlastin) interacts with the DP1 analog in yeast.
Finally, Dr. Blackstone's study notes that Arabidopsis has an analog of
atlastin, called Root Hair Defective 3 (RHD3). Mutations affecting RHD3
cause the plant to grow short, wavy root hairs.
If this connection between axon growth and root hair growth withstands
further study, Arabidopsis could be a useful tool for investigating
mechanisms of HSP. Arabidopsis is easy to raise in the lab, and the short
root hairs of the RHD3 mutant are easy to observe, compared to the growth
defects in atlastin-deficient neurons and yeast. Dr. Blackstone hopes to
collaborate with other researchers to initiate a search for genes and
compounds that correct root hair development in the RHD3 mutant, which might
provide valuable therapeutic insights into HSP.
(HTML version includes photo):
<http://www.ninds.nih.gov/img/neurons_roots_HSP.jpeg>
The photo caption is: Top: Rat cortical neurons. Bottom: Arabidopsis roots.
Left side shows normal neurons and root hairs. Right side shows the effects
of atlastin/RHD3 deficiency, with shortening of both and waviness of root
hairs. Neuron images courtesy of Dr. Craig Blackstone, NINDS. Arabidopsis
images courtesy of Dr. John Schiefelbein, University of Michigan, Ann Arbor.
Reference: Hu J, Shibata Y, Zhu P-P, Voss C, Rismanchi N, Prinz W, Rapoport
TA, and Blackstone C. "A Class of Dynamin-Like GTPases Involved in the
Generation of the Tubular ER Network." Cell, Vol. 138, August 7, 2009.
NINDS <www.ninds.nih.gov> is the nation's primary supporter of biomedical
research on the brain and nervous system. NIDDK <www.niddk.nih.gov> conducts
and supports basic and clinical research and research training on some of
the most common, severe and disabling conditions affecting Americans. The
Institute's research interests include: diabetes and other endocrine and
metabolic diseases; digestive diseases, nutrition, and obesity; and kidney,
urologic and hematologic diseases.
The National Institutes of Health (NIH) -- The Nation's Medical Research
Agency -- includes 27 Institutes and Centers and is a component of the U.S.
Department of Health and Human Services. It is the primary federal agency
for conducting and supporting basic, clinical and translational medical
research, and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and its programs,
visit <www.nih.gov>.
##
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<http://www.nih.gov/news/health/aug2009/ninds-06.htm>.
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