Nav: Home

Protein defect leaves sperm chasing their tails

December 02, 2019

Osaka, Japan - With more and more couples seeking assistance to conceive, the steps required for fertilization are being put under the microscope to identify factors that could enhance fertility. In a study published in the journal PNAS, a team led by researchers from Osaka University describe an exciting breakthrough that may aid in future fertility treatments.

When it comes down to it, sperm have only one job: to fertilize the egg. To do this though, they must first make their way to the fallopian tube, propelled by long tails called flagella. When they near their destination, the sperm become turbo-charged in a process known as capacitation, allowing them to race towards the egg. This enhanced motility is triggered by an influx of calcium ions into the flagellum. While researchers have known for some time that an electrical signal-sensing protein called VSP is expressed in sperm of many animal species, the actual physiological role of this protein was unknown.

Lead author of the study Takafumi Kawai explains, "Determining the physiological role of VSP was the main aim of our study. To do this, we generated a VSP-deficient mouse line so that we could examine VSP-deficient sperm from these animals."

The first thing the researchers noticed was that the VSP-deficient sperm had a greatly reduced ability to fertilize eggs in vitro. Closer inspection showed that the sperm were swimming around in circles during capacitation, meaning that fewer sperm actually made it to their destination. Defective motility suggested a problem with the flagellum, prompting the researchers to examine these structures in more detail.

"Surprisingly, in normal sperm, a lipid molecule called PIP2 is concentrated near the top of the flagellum, closer to the head," says Dr Kawai. "In the VSP-deficient sperm, PIP2 was both more abundant and more widely dispersed throughout the flagellum. We also recorded much higher concentrations of calcium ions in the VSP-deficient sperm."

These findings suggested that VSP plays a major role in ion channel regulation, which ultimately affects motility. The researchers proposed a mechanism whereby VSP is responsible for the polarized distribution of PIP2 in the flagellum. PIP2 then activates potassium ion channels, which indirectly causes a localized influx of calcium ions, enhancing motility. In the VSP-deficient sperm, the dispersed PIP2 causes excessive calcium ion influx which decreases the flexibility of the flagellum, affecting motility.

According to senior author of the study Yasushi Okamura, the discovery of VSP-based regulation of sperm motility has significant implications for male fertility. "We predict that our findings will lead to the development of fertility treatments that enhance sperm motility, increasing the chances of fertilization."
-end-
The article, "Polarized PtdIns(4,5)P2 distribution mediated by a voltage-sensing phosphatase (VSP) regulates sperm motility," was published in Proceedings of the National Academy of Sciences of the United States of America at DOI: https://doi.org/10.1073/pnas.1916867116.

About Osaka University

Osaka University was founded in 1931 as one of the seven imperial universities of Japan and now has expanded to one of Japan's leading comprehensive universities. The University has now embarked on open research revolution from a position as Japan's most innovative university and among the most innovative institutions in the world according to Reuters 2015 Top 100 Innovative Universities and the Nature Index Innovation 2017. The university's ability to innovate from the stage of fundamental research through the creation of useful technology with economic impact stems from its broad disciplinary spectrum.

Website: https://resou.osaka-u.ac.jp/en/top

Osaka University

Related Protein Articles:

Discovery of an unusual protein
Scientists from Bremen discover an unusual protein playing a significant role in the Earth's nitrogen cycle.
Protein aggregation: Protein assemblies relevant not only for neurodegenerative disease
Amyloid fibrils play a crucial role in neurodegenerative illnesses. Scientists from Heinrich Heine University Düsseldorf (HHU) and Forschungszentrum Jülich have now been able to use cryo-electron microscopy (cryo-EM) to decode the spatial structure of the fibrils that are formed from PI3K SH3 domains - an important model system for research.
Old protein, new tricks: UMD connects a protein to antibody immunity for the first time
How can a protein be a major contributor in the development of birth defects, and also hold the potential to provide symptom relief from autoimmune diseases like lupus?
Infection-fighting protein also senses protein misfolding in non-infected cells
Researchers at the University of Toronto have uncovered an immune mechanism by which host cells combat bacterial infection, and at the same time found that a protein crucial to that process can sense and respond to misfolded proteins in all mammalian cells.
Quorn protein builds muscle better than milk protein
A study from the University of Exeter has found that mycoprotein, the protein-rich food source that is unique to Quorn products, stimulates post-exercise muscle building to a greater extent than milk protein.
More than a protein factory
Researchers from the Stowers Institute for Medical Research have discovered a new function of ribosomes in human cells that may show the protein-making particle's role in destroying healthy mRNAs, the messages that decode DNA into protein.
Put down the protein shake: Variety of protein better for health
University of Sydney researchers have examined whether there are any ongoing ramifications or potential side-effects from long-term high protein intake or from consuming certain types of amino acids.
Elucidating protein-protein interactions & designing small molecule inhibitors
To carry out wide range of cellular functionalities, proteins often associate with one or more proteins in a phenomenon known as Protein-Protein Interaction (PPI).
The protein with the starting gun
Whether dormant bacteria begin to reproduce is no accident. Rather, they are simply waiting for a clear signal from a single protein in the cell interior.
Protein moonlighting
A class of proteins involved in essential cell functions has an unexpected role, UCSB scientists discover.
More Protein News and Protein Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#542 Climate Doomsday
Have you heard? Climate change. We did it. And it's bad. It's going to be worse. We are already suffering the effects of it in many ways. How should we TALK about the dangers we are facing, though? Should we get people good and scared? Or give them hope? Or both? Host Bethany Brookshire talks with David Wallace-Wells and Sheril Kirschenbaum to find out. This episode is hosted by Bethany Brookshire, science writer from Science News. Related links: Why Climate Disasters Might Not Boost Public Engagement on Climate Change on The New York Times by Andrew Revkin The other kind...
Now Playing: Radiolab

An Announcement from Radiolab