Nav: Home

Sensory response to environmental stimuli modulated by form of vitamin B3 in worms

October 12, 2016

EMBARGOED: Publication of information about the research described here is prohibited -- in any medium -- by the journal Nature Communications until 5:00 a.m. U.S. Eastern time (1000 BST) on October 12, 2016.

Sensory response to environmental stimuli modulated by form of vitamin B3 in worms

Experiments show that too much of a form of vitamin B3 -- nicotinamide -- that is produced naturally inside of cells can lead to cell death in certain sensory cells and cause behavioral changes in the worm, Caenorhabditis elegans. The research, by a team of Penn State scientists, shows that excess nicotinamide causes overactivity of the TRPV ion channel that is involved in sensory perception by controlling the movement of certain charged particles in and out of cells. The work also provides clues to the mechanism causing the cells to die, and links these cellular processes to behavior. A paper describing the research is published in the October 12, 2016 edition of the journal Nature Communications.

"We didn't set out to study the TRPV ion channel, but we found out that vitamin B3 is having physical and behavioral effects on the worm that we study and when we followed these effects using genetics we found that the nicotinamide form of vitamin B3 is toxic to certain cells that use the TRPV ion channel," said Wendy Hanna-Rose, associate professor of biochemistry and molecular biology at Penn State and the lead author of the study. "We were able to show that nicotinamide is an agonist of the TRPV channel -- it causes it to be overactive -- which causes the cells to die. What's really cool about this is the idea that the TRPV ion channel which is involved in sensory perception -- it responds to things like pain, touch, or temperature changes -- is regulated by a natural byproduct of the cell's metabolism which in turn influences the worm's behavior."

The research team had previously shown that when a gene, pnc-1, that is involved in nicotinamide metabolization in cells is mutated in the worm, nicotinamide can build up to ten times its normal level in sensory cells in the worm's uterus, causing the cells to die. In the current paper, the researchers experimentally expose the worms to excess nicotinamide and identify another type of sensory nerve cell that dies from the resulting overactivity of the TRPV channel.

The two cell types affected by nicotinamide share the expression of the genes osm-9 and ocr-4 -- two of the several genes that encode TRPV ion channel subunits in worms. The researchers labeled these two genes with a fluorescent marker and showed that the overactive TRPV channel in the cells is made up of two copies each of the proteins encoded by these two genes.

"We intuitively understand that metabolism can affect a sensory input -- how good something smells might be affected by how hungry you are -- but we don't know much about how that happens," said Hanna-Rose. "With this research we are opening a door to identifying a mechanism for how a cell's metabolic state can directly affect a sensory channel."

Because the TRPV ion channel is involved in sensory perception, the researchers next explored whether cell death as a result of overexposure to nicotinamide effects the worm's behavior. The nerve cells that die are exposed to the environment through the worm's nose and are used by the worm to sense food while foraging. Worms exposed to excess nicotinamide, either experimentally or by mutation of the pnc-1 gene, expressed an abnormal head-bending behavior while foraging compared to wild-type worms. The researchers also linked an egg-laying defect in the worms to the excess nicotinamide and overactive TRPV channels.

The researchers also showed that the ability of nicotinamide to overexcite the TRPV channel is evolutionarily conserved. They exposed larvae of the fly, Drosophila melanogaster, to nicotinamide and found that the response of the larvae to vibration was reduced. This mirrored the effect of loss-of-function mutations to the fly versions of the TRPV genes, but it did not result in cell death.

"TRPV ion channels are not just evolutionarily conserved in worms and flies," said Hanna-Rose. "These sensory receptors are found in mammals as well -- capsaicin receptors for example -- and many others like them. Our work opens a new avenue for studying the mechanism by which these receptors function, showing that they can be regulated by naturally occurring products of a cell's metabolism"
-end-
In addition to Hanna-Rose, the Penn State research team includes Awani Upadhyay, Adity Pisupati, Timothy Jegla, Matt Crook, Keith J. Mickolajczyk, Matthew Shorey, Laura E. Rohan, Katherine A. Billings, Melissa M. Rolls, and William O. Hancock. The research was supported by the U.S. National Institutes of Health. Hanna-Rose also received support from Penn State's Huck Institutes of the Life Sciences.

CONTACTS

Wendy Hanna-Rose: wxh21@psu.edu, (+1) 814-865-7904

Barbara Kennedy (PIO): science@psu.edu, (+1) 814-863-4682

IMAGE

A high-resolution image is available for downlaed at https://psu.app.box.com/v/HannaRose10-2016 (If captions are not visible, click the horizontal arrow in the small right-most box at the top of the page.)

IMAGE CAPTION and CREDIT

An adult Caenorhabditis elegans worm. A form of vitamin B3, nicotinamide, modulates the worm's sensory response to environmental stimuli. Credit: Kbradnam, https://creativecommons.org/licnses/by-sa/2.5/

TITLE OF RESEARCH PAPER

The title of the research paper that will be published in the journal Nature Communications is "Nicotinamide is an endogenous agonist for a C. elegans TRPV OSM-9 and OCR-4 channel."

ARCHIVE

After the embargo lifts, this information will be archived at http://science.psu.edu/news-and-events/2016-news/Hanna-Rose10-2016

Penn State

Related Cell Death Articles:

Starvation causes atypical cell death
Researchers from IDIBELL -- within the Marie Curie ITN TRAIN-ERs -- have characterized the cell death process due to starvation, in which the endoplasmic reticulum plays a leading role.
An 'IRBIT'uary before cell death
Billions of cells in our bodies die every day in an important process called apoptosis.
APOL1 linked to reduced nephrocyte function, increased cell size, accelerated cell death
A Children's National Health System research team has uncovered a novel process by which the gene APOL1 contributes to renal disease, according to a paper published Nov.
Neurobiology: Epigenetics and neural cell death
Researchers from Ludwig-Maximilians-Universitaet (LMU) in Munich have demonstrated how deregulation of an epigenetic mechanism that is active only in the early phases of neurogenesis triggers the subsequent death of neural cells.
Cell death: How a protein drives immune cells to suicide
For some pathogens, attack is the best form of defense -- they enter immune cells of the human body.
Brain cell death in Alzheimer's linked to structural flaw
Researchers have identified a new biological pathway involved in Alzheimer's disease.
Clarifying the role of CHOP/GADD153 in cell death
In the May 2016 Nature Communications, investigators at the Medical University of South Carolina report that CHOP/GADD153-dependent apoptosis is mediated by the micro-RNA miR-216b.
New insights in cancer therapy from cell death research
Killed cancer cells serve as a potent anti-cancer vaccine Researchers in the group of Prof.
New class of drugs specifically induces cell death in B cell blood cancers
New research from The Wistar Institute shows how one protein found on the endoplasmic reticulum can serve as a target for stimulating the immune system and a more direct target for cellular death in B cell malignancies.
Scientists reveal alternative route for cell death
Researchers at St. Jude Children's Research Hospital have uncovered a new pathway for mitochondrial cell death that involves the protein BCL-2 ovarian killer otherwise known as BOK.

Related Cell Death Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...