Cell biologist and Dartmouth professor of Biology 12, Elizabeth Smith, and her graduate research assistant, Christen DiPetrillo, recently published a paper on a particular protein complex’s role in motility in the green unicellular algae Chlamydomonas reihardtii.

The complex has four flagellar associated proteins, FAP54, 46, 74, and 221.  FAP221 was the main focus of the research because it is very similar to the mammalian Primary Ciliary Dyskenisia Protein 1 (Pcdp1).  Also, it is the only one of the four small enough to interact with calmodulin, which is a protein with a high affinity for calcium.

In their paper, Smith and DiPetrillo mention a claim from an earlier study, which doubted the existence of an orthologue of Pcdp1 based on the Chlamydomonas’s genome.  However the pair  scrutinized the intron-exon prediction for FAP221 and realized that there indeed was a striking similarity between FAP221 and Pcdp1.

Besides the genetic similarity, both FAP221 and Pcdp1 bind calmodulin in the same general region, which involves a calcium-sensitive process.  More important than the structure of the complex, however, is how it aids in motility.

Cell motility is often the result of either ciliary or flagellar beating.  Both of these processes are crucial cytoskeletal components in both unicellular organisms and in humans. In mammals, a mutation of Pcdp1causes Primary Ciliary Dyskenisia and has dire consequences, including “hydrocephalus, [the accumulation of water on the brain], respiratory defects [like sinusitis], and male infertility.”

Smith’s lab studied multiple different mutations of the complex, and discovered that mutants of FAP221 make it unable to interact or bind with calmodulin, as well as with two other members of the complex, FAP54 and FAP46.  Without calmodulin, and thus without calcium, motility is impeded.

They also found that many wild-type (non-mutated) strains of Chlamydomonas have cells with flagella that cannot switch between “asymmetric (ciliar) and symmetric (flagellar) waveforms.”  This implies that the FAP221 complex plays an important role not only in binding calcium, but also for beating (pulsating).

Of course, there are still some questions that remain unanswered.   Smith said that one of the big questions is whether Pcdp1 has “the same interactions and role as FAP221.”  She is currently collaborating with George Witman, who is working on solving this problem with mice, in his lab at UMass Medical School. The article states that defects in Pcdp1 have not been found or studied in humans, but that it will be interesting to see how similar these two proteins are in the big picture.

One other question Smith mentioned is why calmodulin can go from binding calcium in high concentration to binding low concentration; it “switches in the action of the dynein arms” in the central apparatus attached to the flagella, said Smith.  While it is known that calcium definitely affects motility and causes a signal transduction for movement, the change of function in calmodulin remains a mystery.