While I don’t doubt that you have all been eagerly awaiting an update to my ‘Publications’ page, some of you may not have noticed that it has finally arrived. After only about 5 and half years in graduate school, I finally have my very own first-author research article.
Why did it take so long? Believe me, I wish it didn’t. But it turns out that writing the paper takes about the same amount of time as doing all the experiments (I may be exaggerating here, but that’s certainly how it felt). After all the re-writes, peer-reviews, and more re-writes, the beautifully formatted, very sciency-looking version is finally online (in the wonderfully open-access journal PLoS Genetics).
If you’re curious what this paper is about, but have absolutely no desire to read it, you’re in luck! I’m not going to go through a play-by-play with this paper because, while I think the results are really cool, I also feel like I already wrote the thing. But I will summarize why the paper is an important step in our continuing quest to figure out what the hell is going on in the seminal fluid.
When flies, or worms, or cats, or people have sex, the male isn’t simply throwing a bunch of sperm into the female where one of them will hopefully reach an egg. Those sperm have a lot of help from other components of the seminal fluid, including tons of seminal fluid proteins (Sfps). You can’t exactly match up the proteins in flies to their counterparts in people; they have changed too much over time to do that. But, the types of proteins in flies are very similar to the types in humans. I have been working on a specific type of Sfps in my work: proteases.
Proteases are a pretty cool group of proteins. They seem simple enough: they chop up other proteins. But each one has a completely different job. Some turn on proteins by cutting them, others turn proteins off. Some only cut up a single target protein at a predetermined place. Others will chop up anything.
The proteases in my paper, CG11864 and one I’ve named ‘seminase’, appear to have really specific targets, but I still don’t know if they are activators or destroyers (possibly both).
The main points of the paper were these:
- We found what we believe is the first protease cascade in insect seminal fluid.
- Our earlier classification of Sfps into two groups based on when they act (short-term and long-term) is no longer as clear-cut as we thought.
- Proteases might be an important way to quickly start the ball rolling on post-mating effects we see in flies.
Number 1: Protease cascades (where a proteases are used to turn on other proteases that eventually go on to do some job) are an important feature of lots of things that go on in your body that you care about. Blood clotting is a good example: when people are missing one of the proteases in the blood clot cascade, they have hemophilia, and usually bleed to death. At least one protease cascade also exists in human seminal fluid, turning it from a gelatinous goo to more of a liquid several minutes after ejaculation.
Why do we need this cascade, and how exactly does it work? The answer is complicated (read: no one really knows). Many studies suggest it’s important for male fertility, and that sperm will be trapped if the protease cascade doesn’t work properly, though this is still controversial. Studying this protein network in people, or even mice, is a huge challenge. Wouldn’t it be nice if some easy-to-work-with animal, like a fruit fly, also had a protease cascade in the seminal fluid? That way, we could manipulate the cascade to understand how it works and why, and apply that knowledge to other seminal fluid protease cascades. Well, here you go. You’re welcome.
Number 2: This one is much more difficult to see why it’s important. Basically, we had a nice grouping system for our Sfps based on whether they affected the female soon after mating (ie: within 24 hours) or had a more prolonged effect (over many days). And this was working just fine until we found seminase. This protease activates a cascade that affects “short term” proteins, but it is also crucial for the long term usage of sperm in storage. Without this protease, the female will simply forget she still has sperm to use and will go mate with someone else after a few days. This is Not Good for whichever poor male was missing his seminase. So seminase is both short term and long term, suggesting there really aren’t two distinct phases of post-mating female responses.
Finally, number 3: Lots of stuff needs to happen after a mating in flies. The female needs to ramp up egg production, store sperm, use the sperm properly, eat more, sleep less, and lose her libido. All of these things rely on Sfps. Do all the Sfps work independently to do their jobs, or might they all be coordinated somehow?
Though I certainly did not prove this in the paper (there’s a ton more work that needs to be done), we are starting to see a suggestion that proteases (maybe my good friend seminase) might be used as a “switch” to turn everything on at once. Proteases can act really fast, and having a protease cascade means the signal can be quickly and easily amplified. More importantly, a single protease can turn on many different proteins, so you don’t need a separate switch for everything that needs to happen in the female.
Whether this might be applicable to other animals, like us, we’ll have to wait to find out. But I certainly wouldn’t be surprised if it turns out to be very common. All animals that anyone has bothered to look at so far have proteases in the seminal fluid. They’ve got to be doing something.
- Get in my spermathecae!
- A protein in worm semen is an “on” switch for sperm.
- Love is (sometimes) a battlefield.
LaFlamme, B., Ravi Ram, K., & Wolfner, M. (2012). The Drosophila melanogaster Seminal Fluid Protease “Seminase” Regulates Proteolytic and Post-Mating Reproductive Processes PLoS Genetics, 8 (1) DOI: 10.1371/journal.pgen.1002435