How Does a Flagellum Know How Long to Grow?
How does a flagellum know when to stop growing? The short answer is, we don't know. The clues so far available point to sophisticated feedback controls for these outboard motors and other organelles in the cell.
Two scientists at UC San Francisco looked into the question recently in Science, "How Cells Know the Size of Their Organelles". Chan and Marshall discussed several ways cells can monitor the size of their construction sites. Here's a little something that makes you say "wow," pointing to the sophisticated controls that are at work:
In the biflagellate green alga Chlamydomonas, when one flagellum is severed, during its regeneration the other, intact flagellum shortens until the two flagella reach equal lengths, at which point they resume growth together. This equalization of lengths seems to indicate that the cell "knows" how long both its flagella are. (Emphasis added.)The tip of a flagellum is way out there, extending into the outside environment. What brings information from that distant point back to the nucleus, where the parts are constructed? The cell can't see it; it has to get chemical messages from that distant frontier somehow without telegraph lines.
You might recall that in the film Unlocking the Mystery of Life, Scott Minnich said that the cell has a signal transduction system that gets feedback from the environment. That was a decade ago and scientists are still trying to figure out how it works.
Chan and Marshall list five methods a cell could use to monitor and control organelle size. "Reporter" molecules might, for instance, be responsive to time, density, structure or some other aspect of the organelle's growing size or shape. Eukaryotic flagella are built by a complex system called "intraflagellar transport" (IFT). Consider this amazing fact: construction parts are delivered to the tip of a flagellum by tiny carts riding along tracks! These carts travel out to the tip and deliver the cargo, like ore carts in a mineshaft:
The total quantity of IFT material per flagellum is roughly constant. Consequently, the transport rate should be a decreasing function of length, because in longer flagella it takes longer for the motors to reach the tip of the flagellum and deliver their cargo .... Furthermore, disassembly rate is length-independent, mediated by microtubule-depolymerizing kinesins. Combined with the length-dependent assembly rate, this constant disassembly gives a unique steady-state solution for length.... The maintenance of constant total IFT protein per flagellum is critical for this model, and it appears to be the result of length-dependent changes in the size and frequency of IFT train import into the flagellum.Other molecular machines work to disassemble the accumulating flagellar "bricks," leading to a tug-of-war between construction and disassembly. The longer the flagellum, the slower it grows, to the point where assembly and disassembly reach equilibrium. But that's only a partial answer:
As further evidence of flagellar length sensing, the frequency of injection of IFT material into the flagellum from the cytoplasm changes as a function of flagellar length. The motors and associated proteins that drive IFT associate into linear arrays known as trains, and, as a regenerating flagellum becomes longer, the trains become smaller but more frequent. The net effect is that the total number of individual IFT subunits is roughly independent of length, but this is only achieved by having the frequency and size of the trains vary with length. So how does the IFT system know how long the flagellum is?Scientists don't know if the part counts are controlled at the base or the tip, but somehow the information is conveyed back to the nucleus. Interestingly, bacteria and eukaryotes appear to use different methods:
In contrast to eukaryotic flagella, bacterial flagella grow at a constant rate, and it has been proposed that their length is determined by a balance between constant growth and random breakage.But that hypothesis would seem to produce random lengths for bacterial flagella, unless breakage rates are constant. That can't be, because flagellum length is important for function:
The systems that contain dedicated size-sensing pathways tend to be ones for which size plays an obvious part in function. Flagellar length is important for cells to create the appropriate waveform to allow movement. Consequently, length control mutations in Chlamydomonas often show severe motility defects, and homologs to these genes are implicated in several ciliopathies.At this point, we should be feeling overwhelmed by the complexity of a "simple" thing like control of organelle size. Look how many factors are involved! Each possible solution raises more questions. Here's a big question that's mentioned at the end of the article:
As we have shown, there are several ways in which cells can sense and control the size of their organelles. But a common follow-up issue arises: How is the size sensor calibrated, or how is the size set point determined? For example, how does a bacterial cell ensure that its molecular ruler is the appropriate length? Or how have the rates in Chlamydomonas flagellar assembly and disassembly been determined so that the flagella are the correct lengths?In other words, even if scientists eventually figure out how flagellum length is controlled, they haven't identified what "knows" how long the flagellum should be. At this point, Chan and Marshall look for a solution to the all-knowing, all-powerful black box of evolution:
Ultimately, the answers to these questions are likely to involve evolutionary tuning of these mechanisms so that organelle size is optimized to some function.If you know of any observations that show a blind, aimless process capable of producing a finely tuned mechanism that functions like an outboard motor, using sensory feedback from the environment, be sure to let the world know. Publish your results! Besides winning plaudits in precincts of biology, you'll likely revolutionize teaching methods in the engineering and architecture departments as well.
Image: SEM image of flagellated Chlamydomonas (10000×), Wikipedia.