The first time I taught a college biology class, I told my students about the structures of different types of cells. There was our type of cell, the eukaryotic cell, with its nucleus like an egg yolk, a web of cytoskeleton, and the collection of mitochondria, endoplasmic reticulum, Golgi apparatus, vesicles, and other “organelles”. All these things make the eukaryotic cell an orderly and structured place. In contrast, there was the Bacterial cell, which I presented as a featureless bag of enzymes. Nobody at the time had convincingly described any distinctive structure or compartments within a bacterial cell. Organelles and cytoskeletons, I told my students, were strictly eukaryotic features.
I always caution my students that I am going to teach them some stuff that is simply wrong. We have recently learned that most Bacteria have a cytoskeleton, and that it shares its ancestry with the eukaryotic cytoskeleton. We are also finding out that there are several different types of organelles within Bacterial cells. A recent study from Pam Silver’s group shows just how sophisticated Bacterial cell structure can be.
Silver’s group studied a type of Bacterium that does photosynthesis: it uses light to make energy (“photo”) and then takes hydrogen from water and adds it to carbon dioxide to synthesize sugar (“synthesis”).
These bacteria are cylindrical, roughly the shape of a tennis-ball can. The “photo” part of their photosynthesis takes part on the surface of the cell, but the “synthesis” part happens in the cell’s interior. The enzyme that is responsible for starting synthesis, called Rubisco, is not efficient. It is like a factory worker with a specific job to do on an assembly line, such as putting together two widgets to make a bigger widget. But this worker is clumsy about picking up the widgets from his workplace, and once he has them, he’s slow to put them together. Rubisco puts together two widgets: carbon dioxide, and a type of sugar, making a bigger sugar molecule. But Rubisco is bad at picking up carbon dioxide, and once it has it, it’s slow to use it.
If you were the sluggish worker’s foreman, you could try to improve his efficiency by putting that worker in a small room. If you filled that room from floor to ceiling with lots of the widgets he needed, the only thing he could pick up would be work for him to do. If you kept all the other different types of workers and their tools and widgets away, he wouldn’t get distracted. Bacterial cells make these small rooms; they are called carboxysomes, and they are one of the best-studied examples of bacterial organelles.
The carboxysome is a room in the bacterial cell reserved for Rubisco. If the cell is the size of our can of tennis balls, the carboxysome is about the size of a ping-pong ball. The room has a few thousand molecules of Rubisco gluing together carbon dioxide and sugar. The walls of this room are particularly remarkable. They are made of a protein called “Ccm K4”. Ccm stands for “carbon-dioxide concentrating membrane,” and it describes precisely what this protein does: the only things that can enter the carboxysome are sugar and carbon dioxide. Everything that Rubisco sees is work for it to do. Without the carboxysome (for example if the cell can’t make Ccm K4 protein), rubisco is so inefficient that photosynthesis grinds to a halt.
Silver’s group wanted to show that the carboxysome is made of CcmK4 and full of rubisco. So, they made a version of the Ccm K4 protein that glowed red, and a version of the Rubisco protein that glowed green. Looking under the microscope, they saw that the cells they were studying had blobs of the right size, glowing both red and green. This was nice but not particularly surprising, since something similar had been seen in other Bacteria. However, they were surprised to see that the carboxysomes were all precisely lined up, right along the long axis of the cell, and that they were very evenly spaced.
If the bacterial cell were the unstructured “bag of enzymes” that I used to lecture about, then a small object like a carboxysome should move around within the cell by diffusion—the same process that makes a drop of ink disperse in a cup of water. The random motion of molecules would push carboxysomes around, and if there were more than one carboxysome per cell, they should be jumbled around. But the carboxysomes did not move at all: they stayed in their evenly spaced order.
Comparison of these cells with other bacterial cells suggested that they have a cytoskeleton: filaments of proteins that run the length of the cell. There are two different types of protein that make up the cytoskeleton in these cells. When Silver’s group made cells that didn’t have one of these proteins, the cells lost their cylindrical shape; instead of looking like a can of tennis balls, the cells looked like balloons. This protein acted like a spring, pushing out the ends of the cell to make it cylindrical. Their carboxysomes were randomly distributed throughout the cell.
When Silver’s group removed the second type of cytoskeletal protein, called “Par A,” from the cell, they saw something really interesting. The cells were still cylindrical, so the bulk of the cytoskeleton was still present. However, the carboxysomes were jumbled around: in some cells, they were clumped together in the middle, in others, there was a pile of carboxysomes at one end or the other. The Par A protein somehow aligns and spaces the carboxysomes.
Par A is a very busy protein; each Par A molecule spends energy moving itself from one end of the cell to the other, then back again; it’s as if Par A has no purpose but to wander back and forth. The cell makes thousands of molecules of Par A, and all these molecules move essentially in unison, like a crowd of people shuffling en masse from one end of a hall to the other, with a round trip taking about two hours. Par A proteins have been seen in many other rod-shaped bacteria without carboxysomes, but Silver’s group was surprised to see that there was a lot of Par A protein oscillating between each of the carboxysomes in a cell. If Par A molecules get stuck between carboxysomes, they still wander back and forth, but over a much shorter distance. The Par A that Silver’s group observed ping-ponging between carboxysomes is enough to nudge the carboxysomes apart. In the time it takes for most Par A molecules to make a round trip of the length of the cell, enough accumulates between carboxysomes to make them evenly spaced.
Why should a cell spend so much energy to arrange the carboxysomes so precisely? Silver’s group addressed this question by studying the cells that didn’t have Par A protein. Because they had a random arrangement of carboxysomes, when the cell divided there was a significant chance that one of the resulting cells would not have any carboxysomes. These cells could eventually make new carboxysomes, but they would grow much more slowly. So, one generation’s energy investment in making organelles and arranging them pays off in the next generation.
There’s at least one thing that’s much more important to the survival of the cell than a carboxysome—the cell’s DNA. It turns out that a Par A system can be used to push one copy of the cell’s DNA to each end of the cell before the cell divides. The name “Par A” is actually short for “DNA partitioning protein A”. Silver speculates that the mechanism for arranging carboxysomes evolved from the DNA partitioning system, since they both make sure that each of the products of cell division gets a necessary feature. What’s more, this Bacterial Par A protein is similar to the protein, actin, that makes up much of the cytoskeleton in Eukaryotic cells. Some sort of cytoskeleton was probably a feature in the last common ancestor of all living things.
So, if any of my 1998 students are reading this, please revise what I told you about Bacteria. They are not just bags of enzymes. Many have cytoskeletons and organelles—they’re even more like you and me than we thought.
David F. Savage, Bruno Afonso, Anna H. Chen, Pamela A. Silver (2010). Spatially Ordered Dynamics of the Bacterial Carbon Fixation Machinery. Science 327, 1258-1261.