2023-10-27 19:45:23
Scientists have unraveled the ins and outs of how sperm go from passive spectators to dynamic swimmers. This transformation is a critical step in your journey toward fertilization and depends on the activation of a unique ion transporter.
Let’s imagine sperm as little adventurers in search of the ultimate treasure: the egg. They don’t have a map, but they use something even more extraordinary: chemoattractants. These are chemical signals released by the egg that act as siren songs, activating and guiding the sperm. When these signals bind to receptors on the surface of the sperm, a series of events is triggered that initiates the movement of the sperm toward the egg. And in this intricate scenario, a key player is a protein known as “SLC9C1.”
This protein is found exclusively in sperm, and under normal conditions it is not active. However, when chemoattractants interact with the surface of the sperm, everything changes.
SLC9C1 works as a very sophisticated exchange system. It exchanges protons from inside the cell for sodium ions from outside, temporarily creating a less acidic environment inside the sperm. This change in the internal environment causes an increase in sperm motility.
SLC9C1 activation is driven by a voltage change that occurs when chemoattractants attach to sperm. To do this, SLC9C1 uses a unique feature called the “voltage sensing domain” (VSD). Typically, VSD domains are associated with voltage-gated ion channels. But in the case of SLC9C1, it is something truly exceptional in the world of conveyors.
A team including Hyunku Yeo and David Drew from Stockholm University in Sweden has unlocked the secrets of the inner workings of SLC9C1 and provided the first example of VSD domain activation of a transporter and its connection via the helix. S4 which acts as a voltage sensor.
The VSD domain responds to the voltage change by pushing its S4 helix inward. This clears the way for ion exchange by SLC9C1, ultimately initiating sperm motility.
The chemoattractant bound to the sperm causes a voltage change, which activates the SLC9C1 transporter. The structure of SLC9C1 has been described for the first time. Once activated, the SLC9C1 protein exchanges protons for sodium ions and this makes the sperm flagellum more alkaline and, together with cyclic adenosine monophosphate (cAMP), leads to the opening of Ca2+ channels resulting in movement. directed from the sperm. This sequence of events, present in species as distant as coral and humans, is essential for fertilization. (Illustration: Ved Mehta / Stockholm University)
“Transporters work very differently than channels, and as such, VSD couples to sperm protein in a way we have never seen or even imagined before. It’s exciting to see how nature has done it, and perhaps, In the future, we can learn from this to make synthetic proteins that can be activated by voltage or develop new male contraceptives that act by blocking this protein,” says Drew.
The study is titled “Structure and electromechanical coupling of a voltage-gated Na+/H+ exchanger”. And it has been published in the academic journal Nature. (Source: NCYT from Amazings)
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