Sunday, July 25, 2010

The Protozoan Inside Us

If you've ever looked through a microscope anytime in biology class you've seen cilia. Cilia are the tiny hairs that cover some cells and enable movement. Often, the example is a protozoan and often those protozoans are Paramecium. If there's a single "hair" it's calls a flagellum. If there are a lot, they're are called cilia. A single hair among cilia is a cilium. The plural of flagellum is flagella. Thus, we dispense with psuedogreek.

But cilia aren't limited to protozoans. The movement of invading particles out of the lungs is accomplished by cilia. Cilia are rendered still or damaged by nicotine, another of the many blessings of cigarettes. Sperm, desperately seeking ovum, wend their desperate way by use of a flagellum.

Peter Satir has been studying cilia since the sixties. The Scientist has a lovely retrospective article about his research here. I'm not going to follow his history here-- which is very interesting and I recommend it. Instead, I want to pull out some gems for my own nefarious purposes.

The moving cilia structure is a means of converting chemical energy (ATP) into kinetic energy. Each cilia is composed, in part, of microtubules. These microtubules slide across one another to create the motion. The energy of the motion is supplied by the ATP. The protein dynein is used for this purpose.

Dyneins, actins, kinesins and myosins are all motor proteins. (See also here.) Myosins are used in vertebrate muscle. They "walk" along actin threads to generate large level contractions. Myosins are also used in cytoplasmic streaming allowing movement of cytoplasm and organelles to different areas of the cell.

Kinesins are a group of related proteins that also walk a microtubule track. They're important in chromosome migration during cell division and also, along with myosin, allow moviment of organelles through the cytoplasm in eucaryotic cells.

All of these molecular motors function in a mechanically similar means: a particular protein slides along a microtubule to effect motion.

However, things get even more interesting in non-motile cilia. Satir soon discovered that the moving cilia were only the obvious ciliary cells. It turns out that the ciliary structure is replicated over many cell types that have nothing to do with movement. The hair cells of the inner ear have cilia.

Which makes sense from an engineering perspective. If it takes energy to move a cilium than it also makes sense that moving a cilium can result in energy generation-- or, to be more precise, if we can transform chemical energy into movement in one direction we can transform kinetic energy back into chemical energy. In the latter direction, we have a sensor.

But the kidney tubule cells also have cilia. Other cell types where non-motile cilia have been found include smooth muscle cells, fibroblasts, neurons and Schwann cells. Stunting the kidney cells caused polycystic kidney disease.

Further, the road to cell differentiation in the developing embryo was lined with cilia.

Cell differentiation is the mechanism by which cells specialize. Embryonic cells turn from a general cell from which (presumably) a total organism could be derived to a specialized cell type for the given organ tissue. One aspect of this process is the migration of cells to their indicated location. Christensen, a fellow of Satir, investigated how a specific cilium could direct cell migration in fibroblasts. They discovered a specific receptor for growth factor became localized to the cilium. When the cilium detected the growth factor, it induced the cell to follow it. The cilium, by virtue of pointing outwards from the cell, actually indicated the direction of migration.

They also showed that cilia was responsible for initiating signals for cell migration in the development of brain and spinal cord.

Very interesting, you say?

Yes, in and of itself.

Stepping back, however, there's another aspect to this.

Cilia are ancient. The development of cilia in green algae (Chlamydomonas) is the same process as the development of cilia in human beings. However, the green algae diverged from the line that produced us at least 1.5 billion years ago-- that's the age of the earliest fossils. (See here.) It is highly unlikely that the identical biochemical mechanism would evolve twice, suggesting that the mechanism was in place prior to that. Prior to the evolution of multicelled organisms.

Evolution always works with the materials at hand and repurposes them to fit the selection criteria of the moment. It makes much more sense to bend something to fit that you already have then to create something out of whole cloth. This happens over and over again. Something that had one use is bent into another one.

Perhaps we all should be listening to our inner paramecium.

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