A Self-Regulating Recycling System Found in the Cell 10/07/2003
Cells are not watertight sacks; they import and export things. But they are not leaky sacks either: everything coming and going is authenticated by sophisticated mechanisms. Small packages, like water molecules or individual proteins, have specially-designed channels embedded in the cell membrane that check their credentials and make them run an electronic gauntlet (see 03/12/02 headline, for instance). Larger packages, however, have a surprising method of making their entrance: they dive in and get wrapped in geodesic spheres. The cell membrane neatly reseals itself around the point of entry, which occurs only where specialized receptors allow it. This is called endocytosis (for cargo on the way in) and exocytosis (on the way out).
The geodesic spheres are made up of a three-armed protein called clathrin. The clathrin molecules envelop the cargo, forming a crystalline sphere. (You absolutely have to see this cool animation by Allison Bruce of Harvard, showing clathrin forming a spherical vesicle; incredible.) Once the cargo in its crystalling sphere has been safely ferried to its destination, the clathrin molecules disassemble and are available for re-use. This process is beautifully illustrated in the award-winning animated short film Voyage Inside the Cell. Exocytosis is the process in reverse, when the cell needs to export cargo to the outside: for example, when a nerve cell needs to send neurotransmitters to another neuron. A host of helper enzymes are involved in making both processes work.
“Clathrin-mediated endocytosis is one of the primary mechanisms by which eukaryotic cells internalize nutrients, antigens, and growth factors and recycle receptors and vesicles,” begin a team of Pennsylvania scientists in a paper in the Oct. 3 issue of Cell.1 But it should be obvious that the amount of cargo coming in must balance that going out, or else the cell will burst or shrivel. “A tight balance between synaptic vesicle exocytosis and endocytosis is fundamental to maintaining synaptic structure and function,” they write, speaking especially of neurons that execute these processes continuously in the central nervous system and the brain. How can the cell maintain this balance?
These scientists discovered an automatic regulatory process that ensures the materials are recycled properly. A protein called endothilin, a key regulator of the endocytosis process, has two states: open and closed. In the open state, it attaches to the interior side of voltage-gated calcium channels (these are membrane turnstiles that allow only doubly-ionized calcium to pass through). Here, it somehow recruits other protein machines needed for the endocytosis operation. When the calcium concentration reaches 1 micromolar, the endophilin switches into the closed position. Then, it detaches from the calcium gate, “which would presumably allow the liberated endophilin and dynamin [another helper enzyme] to become actively involved in endocytosis immediately after SV [synaptic vesicle] exocytosis.” A similar self-regulating system had been known for exocytosis, but this is the first time a mechanism has been found to regulate endocytosis: “By coupling tightly to both the exocytotic and endocytic machineries,” they conclude, “voltage-gated Ca2+ channels are thus uniquely positioned to coordinate the SV recycling process.” Their model, however, is just a rough picture of a much more elaborate process scientists are just beginning to understand. 1Yuan Chen et al., “Formation of an Endophilin-Ca2+ Channel Complex Is Critical for Clathrin-Mediated Synaptic Vesicle Endocytosis,” Cell Vol 115, 37-48, 3 October 2003.
What can you say but “Wow!” Cell operations are so amazing. The authors use the word machinery 14 times, and not once use the word evolution or give any clue how all these parts “emerged” from any simpler cell.
All the parts of this system have to be present and functioning: the voltage-gated calcium channels (voltage-gated: imagine that!), the endothilin and dynamin and other helper enzymes, the clathrin, and much more. Mechanisms must ensure that only authenticated cargo is allowed in, and that the breach is resealed rapidly without leakage. The helpers have to be recruited to the spot ahead of time, so they are ready for the operation. The endothilin enzyme has to have the right shape to open and close when the concentration of calcium is just right. The ingredients must be recycled and kept in balance.
Each component is a complex system in itself. Each protein is a large molecule of precisely-sequenced amino acids. This is a system of complex systems. How could such a smooth, efficient, functional system evolve? A mutation in just one component can break the whole process: in fact, that’s how they learned about it, by artificially mutating a component, which drastically impaired the operation.
Pause and wonder: you can read and think about this right now because endocytosis and exocytosis is going on in your brain millions of times a second.
[COMMENT: Can't you see this cell evolving by accident? There are probably a dozen examples of "irreducible complexity" involved here at least. I.e., complexity which must (as indicated above) be wholly in place to function at all, and which cannot be built up by incremental steps.
E.g. - something as simple as a mouse trap. You cannot begin with a spring and catch a few mice, and then add the spring to a board (so it actually "springs") and catch a few more, and then add the cheese holder to catch a few more, and then the cheese to catch a lot. You have to have them all there to catch any at all. A mouse trap cannot evolve incrementally, it must be designed by someone who knows what he is aiming for and the principles to be employed.
A tornado in a junkyard will not produce a Boeing 747 no matter how long it spins the air.
Just so, the cell. The chances of it evolving are so far outlandish as to be (I would guess) beyond the limit of what statisticians call "impossible", where the odds are so infinitesimally small as to be essentially zero. For example, some of the odds I have heard for something like this to happen are 1 out of <some number greater than the number of atoms in the whole universe>. And the more we learn, the more we see now "absurdly" complex things are. The rational meaningfulness of evolution is evaporating the more we learn about the complexity of the empirical world. And this is only for starters.
If one wants to take his chances on those sorts of numbers being meaningful explanation over the Biblical view of God, let him have at it. E. Fox]
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