The human nose has millions of olfactory neurons grouped into hundreds of different neuron types. Each of these neuron types expresses only one odorant receptor, and all neurons expressing the same odorant receptor plug into one region in the brain, an organization that allows for specific odors to be sensed.
For example, when you smell a rose, only those neurons that express a specific odor receptor that detects a chemical the rose emits get activated, which in turn activates a specific region in the brain. Rotten eggs on the other hand, activate a different class of neurons that express a different (rotten egg) receptor and activate a different part of the brain. How the one-receptor-per-neuron pattern — critical for odor discrimination — is achieved in olfactory neurons is a mystery that has frustrated scientists for long.
Now a team of scientists, led by neurobiologists at the University of California, Riverside, has an explanation. Focusing on the olfactory receptor for detecting carbon dioxide in Drosophila (fruit fly), the researchers identified a large multi-protein complex in olfactory neurons, called MMB/dREAM, that plays a major role in selecting the carbon dioxide receptors to be expressed in appropriate neurons.
Study results appear in the Nov. 15 issue of Genes & Development. The research is featured on the cover of the issue.
According to the researchers, a molecular mechanism first blocks the expression of most olfactory receptor genes (~60) in the fly's antennae. This mechanism, which acts like a brake, relies on repressive histones —proteins that tightly wrap DNA around them. All insects and mammals are equipped with this mechanism, which keeps the large families of olfactory receptor genes repressed.
"How, then, do you release this brake so that only the carbon dioxide receptor is expressed in the carbon dioxide neuron while the remaining receptors are repressed?" said Anandasankar Ray, an assistant professor of entomology, whose lab conducted the research. "Our lab, in collaboration with a lab at Stanford University, has found that the MMB/dREAM multi-protein complex can act on the genes of the carbon dioxide receptors and de-repress the braking mechanism — akin to taking the foot off the brake pedal. This allows these neurons to express the receptors and respond to carbon dioxide."
Ray explained that one way to understand the mechanism in operation is to consider a typewriter. When none of the keys are pressed, a spring mechanism or "brake" can be imagined to hold the type bars away from the paper. When a key is pressed, however, the brake on that key is overcome and the appropriate letter is typed onto the paper. And just as typing only one letter in one spot is important for each letter to be recognized, expressing one receptor in one neuron lets different sensor types to be generated in the nose.
"If this were not the case, a single cell would express several receptors and there would be no diversity in sensor types," Ray said. "Our study then attempts to answer a fundamental question in neurobiology: How do we generate so much cellular diversity in the nervous system?"
Next, the researchers will test whether the receptor-braking mechanism they identified in Drosophila is also involved in other organisms like mosquitoes. They also will examine the other receptors in Drosophila to explain what de-represses each one of them.
Modulating response levels
The researchers also found that the activity of the MMB/dREAM multi-protein complex in Drosophila can alter levels of the carbon dioxide receptor and modulate the level of response to carbon dioxide.
"If you dial down the activity of the complex, you also dial down the expression of the carbon dioxide receptors, and the flies cannot sense carbon dioxide effectively," Ray said. "What's particularly encouraging is that this complex is highly conserved in mosquitoes as well, which means that we may be able to dial down the activity of this complex in mosquitoes using genetic strategies, and potentially lower the ability of mosquitoes to sense carbon dioxide, used by them to find human hosts. Because carbon dioxide receptors are so well conserved in mosquitoes, we expect that the regulatory mechanism we discovered in Drosophila may also be acting on mosquito carbon dioxide receptors."
Antenna versus maxillary palp
Interestingly, flies sense carbon dioxide with receptors located in their antennae, and avoid the source. Mosquitoes, on the other hand, are attracted to carbon dioxide and use receptors located not on their antenna but another organ called the maxillary palps (small structures present near the mouthparts). The research team found that two specific proteins in the multi-protein MMB/dREAM complex in mosquitoes have sequences that are quite different from those of the corresponding proteins in Drosophila.
"These proteins — E2F2 and Mip120 — could explain why Drosophila expresses carbon dioxide receptors in the antennae while the mosquito expresses them in its maxillary palp," Ray said.
The research done in Ray's lab was funded by a grant to Ray from the Whitehall Foundation. Besides Ray, UCR's Sarah Perry, the research paper's co-first author and a graduate student in the Genetics, Genomics and Bioinformatics program, and Sana Tharadra, a junior specialist in Ray's lab were involved in the research. They were joined in the work by Stanford University's Choon Kiat Sim, the co-first author of the research paper, and Joseph S. Lipsick, a professor of pathology and genetics.
The University of California, Riverside is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UCR's enrollment has exceeded 21,000 students. The campus will open a medical school in 2013 and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Center. The campus has an annual statewide economic impact of more than $1 billion. A broadcast studio with fiber cable to the AT&T Hollywood hub is available for live or taped interviews. UCR also has ISDN for radio interviews. To learn more, call (951) UCR-NEWS.
Iqbal Pittalwala | EurekAlert!
What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
06.12.2016 | Health and Medicine
06.12.2016 | Life Sciences
05.12.2016 | Power and Electrical Engineering