Science: Significant advances In micro-tube protein glycosylation controls sperm movement mechanisms

In a new study, researchers from research institutions such as the Curie Institute in Paris, the Cotchin Institute in Paris, the Max Planck Institute for Molecular Cell Biology and Genetics in Germany, the University of Bonn and the Centre for Human Technology in Milan, Italy, have now discovered that a special enzyme modification called glycation is key to keeping sperm moving in a straight line.
suggest that interfering with this modification may be the root cause of some forms of male infertility in humans.
published in the January 8, 2021 issue of the journal Science, under the title "Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility."
cells in our bodies use our DNA library to extract blueprints that contain instructions for building structures and molecular machines called proteins.
but the story doesn't end there: proteins can be modified by enzymes.
the occurrence of such modifications has long been known, but surprisingly their function is not known in many cases.
example of our lack of in-depth knowledge is the role played by micro-tube protein modification.
tubes are long wires used to make stents in cells.
tubes are highly similar to all cells in our bodies, they perform a variety of functions.
of the most specialized functions of micro tubes are found in the sperm tail or whiplash.
sperm whiplash is essential for male fertility and sexual reproduction.
they have to beat in a very precise and coordinated way to allow sperm to swim gradually, which, if not done, can lead to male infertility.
in order to keep sperm moving in a straight line, enzymes are essential for the modification of micro-tube proteins.
one of these modifications, called glycosylation, is by far the least explored of micro-tube protein modifications.
the researchers studied sugar-basedization carefully.
found that without this micro-tube protein modification, the way the whiplash beats can be disrupted, causing sperm to swim mostly around in circles. "The core of sperm whiplash is made up of micro tubes, as well as tens of thousands of tiny molecular motors called dynein, which bend these microns rhythmically, creating waves of motion and steering," explains Sudarshan Gadadhar of the Curi Institute in Paris, the lead author of the
paper.
activities of these power proteins must be closely coordinated.
in the absence of glycosylation, they become incohergic, and as a result we suddenly see sperm swimming around in circles.
to find out, the researchers developed a mouse line that lacked the enzymes that glycosylated the micro tubes.
, co-author of the paper and a researcher at the Curie Institute in Paris, said, "We observed functional deficiencies in sperm in mice with a lack of glycosylation in the micro-tubes, leading to a decline in fertility."
similar defects in humans can lead to male infertility because mice that act as model systems are known to have strong fertility.
To find out why a lack of glycosylation interferes with sperm motor activity and male infertility, the researchers used cryogenic electron microscopes to visualize the molecular structure of sperm whiplash and its molecular motors.
analysis of the mutant sperm whiplash showed that the whiplash was properly constructed, but the mutation interfered with the coordination of the fibre-haired shaft-powered protein --- a molecular motor --- that powers the whiplash beat.
explains why sperm cells are disturbed by swimming.
why is this discovery so important? "This study shows how important glycosylation is to control the power proteins of whiplash and is a classic example of how micro-tube modification directly affects the function of other proteins in cells," concluded Luis Alvarez of gaia Pigino of the Max Planck Institute for Molecular Cell Biology and Genetics and the European Centre for Advanced Studies, who co-authored the paper.
our results provide direct evidence that micro tubes play an active role in regulating basic organisms by modifying the code through micro-tube proteins.
, the study also points to a new mechanism of male infertility.
because sperm whiplash is one of the many types of culver hair in our bodies, we expect similar micro-tube protein modifications to be important in a variety of fiber-related functions.
, our research opens the door to an in-depth understanding of a variety of diseases, such as developmental disorders, cancer, kidney disease, or respiratory and visual diseases.
" Reference: 1.Sudarshan Gadadhar et al. Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility. Science, 2021, doi:10.1126/science.abd4914. 2.Keeping sperm cells on track