Protein Angst

Monday, December 12, 2005

Nick and Nora, Sid and Nancy, Notch and Delta

Hey, science lovers! I'd like to point out that Dr. K. George Chandy himself commented on my last post. He provided the link for the paper ("K+ channels as targets for specific immunomodulation") if you're interested in his work.

But that's old news! Today's news is this: signaling pathways are hilarious. One of my favorites is Notch/Delta.

Notch and Delta are proteins in Drosophila. All the cool stuff happens in fruit flies. Of course, the cool stuff happens in humans too; we just call the players by less cool names.

Notch and Delta are a receptor and a ligand, respectively. Delta is the baseball that fits into Notch's mitt. But why are we playing baseball in the first place?

See, when two fruit flies really love each other...well, you know the rest. Their little bundle of joy is going to need a nervous system. During the early stages of development, though, the cells are all kind of the same because they don't know what to do. They don't know what to become. They have not been given their life's ambition, their purpose.

Let's take a look at one such cell. Call her Veronica. Veronica is destined to become a mechanosensory bristle on the body of Lil' Fly. You know, the little touch-sensitive hairs. Veronica really, really wants to be a bristle, but first, she has to out herself as the sensory mother cell (SMC). Now she knows that if she becomes an SMC, the cells around her (let's call them Duncan, Troy, Leo, and Logan) can't be SMCs as well. You don't want a fruit fly that's one big hairy bundle of bristles.

Duncan and the boys kind of want to end up bristles too, though. Being a bristle is a pretty sweet gig. You get to react to the environment and let the fly know what's going on. It's an important job!

Now, all of our cells here are expressing Delta, just throwing it out like a pop fly (no pun intended). And they've also got Notch on the surface, all, "I've got it! I've got it!"

But here's the deal: if Notch catches Delta, it becomes activated. And it tells the cell not to become an SMC. It gets better, though, and this is the hilarious part: it throws out less Delta. See, the only way it has a fighting chance of becoming an SMC is if it keeps the cells around it from throwing out so much Delta. And the only way to do that would be to activate Notch in them so that they throw out less Delta. And the only to do that would be to throw out more Delta. EXCEPT IT CAN'T AHAHAHAHAHA.

Troy can try all he wants to toss out enough Delta to become king of the hill. They can all try; it's fun and in the spirit of competition. But the very instant Veronica gets the advantage (and she will, because it's her destiny), the game is over. Because she throws out more Delta, the boys throw out less Delta, which means fewer of her Notch receptors are activated, allowing her to throw out even more Delta. All their Notch receptors are hella activated, and hers just sit there inactivated like whoa. This is called lateral inhibition: she's keeping all the adjacent cells from following the same path she is. And it's nothing personal, guys! It would be dangerous and catastrophic for the full organism! You've got to take one for the team. Being an epithelial cell is still kinda cool.

I mean, not as cool as being a bristle, but still.

So that's Notch/Delta in a nutshell. It's a harrowing tale of power struggles, establishing dominance, and kicking cells when they're down.