Flying To The Tune Of A Neuropeptide Receptor: “Exciting” Insights From Fruit Flies

For a fruit fly, flying is just about everything. It is the most important innate behavior that helps the fly reach out to food sources and mates, escape predators, and find secure sites to lay eggs. But what gives the fruit fly its ability to fly relentlessly and reach out to your fruit bowl? A recent study from the lab of Prof. Gaiti Hasan, published in PLOS Genetics, has identified molecules that play a key role in this behavior.

Flying, as many believe, demands tremendous energy. But did you know that the underlying basis for initiating and maintaining flight largely depends on the activity of neurons? Any visual, odor, or mechanical cue to a fly is perceived by peripheral sensory neurons, which then transmit this information to deeper brain centers. Specific neurons in the central brain of the fly respond to these stimuli and convey the messages further down to the central pattern generator that enables the coordinated action of flight muscles for flight.

Image credit: Preethi Ravi

So, how long can flies fly? Under lab conditions, the authors have observed that tethered flies can fly on average for about 10 minutes, uninterrupted! This paradigm has been used to identify neurons and molecules that help maintain such long flight bouts and which could prove an advantage for the flies’ survival in the wild.

The authors have discovered that a protein called the FMRFa receptor (FMRFaR) plays an important role in fly neurons to enable flight for long periods of time. FMRFaR resides on the plasma membrane of cells and is classified under a group of proteins called G-protein coupled receptors (GPCRs). GPCRs transduce extracellular messages from molecules such as peptides, hormones, and neurotransmitters into intracellular responses. What happens when a fruit fly lacks this protein FMRFaR? The authors found that flies mutant for the FMRFaR were unable to fly for long. In fact, these flies could only maintain flight for half the time as that of their wild-type counterparts. The question, then, is where exactly are these proteins present and what do they do.

Just like humans, fruit flies have a variety of neurons in their brain that make different neurotransmitters for conveying information to each other. Among them are a well-known class of neurons that make and use dopamine for signaling. Dopaminergic neurons, as they are called, are known to affect behaviors such as learning, memory, and locomotion in mammals. In the fruit fly, genetic experiments revealed that FMRFaR was present in mature dopaminergic neurons, and flies with neurons that lacked the FMRFaR in adults were only able to maintain flight for less than 3 minutes.

How does FMRFaR on fly dopaminergic neurons help sustain flight? FMRFaR, upon activation, initiates a signaling cascade within cells that elevates cytosolic calcium, a process required for regulating neuronal excitability. Neuronal excitability is the change in the membrane potential of neurons that occurs through the influx and efflux of ions such as sodium, potassium, and calcium. These changes depolarize neurons and stimulate the release of signaling chemicals called neurotransmitters that convey signals from a neuron to its partner neuron(s).

Ravi et al. found that FMRFaR function is required in dopaminergic neurons to maintain optimal excitability. Loss of FMRFaR in mature dopaminergic neurons decreased their ability to depolarize as measured by fluorescence intensity of a protein that responds to changes in membrane potential. Conversely, when dopaminergic neurons lacking the FMRFaR were genetically supplemented with a protein that increased membrane excitability flies showed significant improvement in the duration of flight bouts. These findings demonstrated that the FMRFaR in dopaminergic neurons is required for regulating membrane excitability and thereby flight.

The question that follows then is how does FMRFaR alter neuronal excitability? Stimulation of the FMRFaR results in the production of inositol trisphosphate (IP3), a small molecule, which binds to a protein present on the endoplasmic reticulum, named Inositol-trisphosphate receptor (IP3R). The IP3R is also an ion channel and upon binding IP3, it releases calcium from the endoplasmic reticular stores and thereby increases cytosolic calcium. This calcium can activate calcium-sensitive proteins. One such protein is the Calcium-calmodulin dependent Protein Kinase (CaMKII). Shorter flight bouts in flies with reduced CamKII function in dopaminergic neurons led the authors to speculate that CaMKII is activated in response to FMRFaR stimulation in neurons. Indeed, the flight deficits due to FMRFaR loss in dopaminergic neurons were ameliorated to an extent by over-expression of CamKII. They believe that the calcium elevation following FMRFaR activation stimulates CamKII that in turn either directly or indirectly influences channels on the plasma membrane that control neuronal excitability.

Overall, it seems like the FMRFaR is at the interface of extracellular and intracellular calcium signaling in dopaminergic neurons and such signals help maintain the membrane potential of dopaminergic neurons in a state required for sustained flight. The identity of membrane channels that are sensitive to FMRFaR activation is still unknown. Though it is known that the FMRFaR is activated by a neuropeptide called FMRF, neurons that release FMRF and signals that stimulate FMRF release also remain to be identified.

These findings are described in the article entitled FMRFa receptor stimulated Ca2+ signals alter the activity of flight modulating central dopaminergic neurons in Drosophila melanogaster, recently published in the journal PLOS Genetics. This work was conducted by Preethi Ravi, Deepti Trivedi, and Gaiti Hasan from the National Centre for Biological Sciences, Tata Institute of Fundamental Research.

About The Author

PR
Preethi Ravi
Gaiti Hasan

Gaiti Hasan is an Indian scientist who researches in the fields of molecular biology, genetics, neuroscience and cell signalling. Hasan is a Fellow of the Indian National Science Academy (INSA), the apex body of Indian scientists and technologists. 2013 onwards she has been serving as a Senior Professor at the National Centre for Biological Sciences (NCBS), Bangalore.

Speak Your Mind!

READ THIS NEXT

Gigantic Iron Mass Transfer In The Early History Of The Earth/Mars: Ferrous Iron Borate Aqueous Complex As A Key Player In Primitive Earth/Mars Oceans?

Iron is the fourth-most-abundant element in the Earth‚Äôs crust. There were massive movements of iron in primitive oceans in the early history of our Earth, resulting in the formation of impressive iron deposits called Banded Iron Formations (BIF) in geology. Our current civilization is largely built on the utilization of such iron deposits. In the […]

Finding Frankenflora: Using Sanger Sequencing To Identify Protea Hybrids

‚ÄúFrankenflora‚ÄĚ are swarms of hybrid plants that are the result of species being translocated outside of their natural ranges. The name was first coined by Tony Rebelo in 2005 to refer to hybrids in the Proteaceae family that result in a loss of species diversity. These ‚ÄúFrankenflora‚ÄĚ then become the dominant community game changers. Rebelo […]

Female And Male Gamete Cells: Called Sex Cells

Gamete cells, also known as sex cells, are the cells responsible for sexual reproduction. A male gamete is called sperm (spermatozoa) and is a haploid cell formed through¬†Spermatogenesis. A female gamete is called an ova or egg cells (Oocytes), which are haploid cells carrying one copy of each chromosome. Gametes are necessary for DNA to […]

Climate Change And Estuaries: C, N, and P Retention Fluxes

Estuaries serve many important functions ‚Äď they provide recreational opportunities for coastal populations, host important fisheries (including oysters, blue crabs,¬†and striped bass), and support a diverse food web that contains species from both the freshwater and marine realms. The mixing of marine and freshwater creates unique conditions and high rates of biogeochemical activity. Ecosystem ecologists […]

Deposition Definition In Science

Deposition, by definition in chemistry, refers to a phase transition in which matter transitions¬†directly from a gaseous state into a solid state without passing through an intermediate liquid phase. Deposition is the opposite of sublimation, a phase transition in which a solid transitions directly into a gas. Deposition and sublimation are 2 of the 6 […]

Researchers Study How Long Microorganisms Can Survive On Mars

By the year 2026, Russia and the United States hope to begin the construction of a space station to orbit the Moon. This project would mark the beginning of a new age of space exploration as the station will be used as an intermediary between Earth and the rest of the solar system. With the […]

NASA Puts The Finishing Touches On The Next Mars Lander InSight

The next Mars lander, InSight, is currently¬†preparing for its upcoming launch in May by deploying its solar panels inside Lockheed Martin’s lab in Colorado. With InSight’s slated launch in a few months, we figured we would go over just what InSight is and what it will do for our understanding of Mars. Studying whether there’s […]