The beginning of the end of flagella

Protein discovery in Chlamydomonas

A new protein discovery sheds light on how chemical information is transported within cells. A group of researchers, which includes Dartmouth Professor of Biological Sciences Roger Sloboda, have found the protein EB1 in Chlamydomonas, a single-celled organism commonly used to study cell biology. Previous research has implicated EB1 in the progression of many colon cancers.

Published in the November 11 edition of the journal Current Biology, the research examined the chemical motors that power events in flagella, antenna-like structures on some cells. Specifically, the research focused on intraflagellar transport (IFT), the process where proteins required for flagellar growth and maintenance move within the flagella. The discovery of the protein EB1 at the tip of the flagella on Chlamydomonas furthers investigations into the role the protein plays in flagellar function and perhaps in regulating IFT itself.

“Particles move out to the tip of the flagella, turn around, and then move back to the base,” says Sloboda, who conducted this research in Joel Rosenbaum’s laboratory at Yale University while on sabbatical last year. “The only change in speed or direction occurs when the particles reach the tip. Now we think EB1 might play a role in controlling the molecular transport system responsible for IFT when the particles reach the tip. This finding will help us get a handle on what’s going on at the tip of the flagellum.”

The flagella beat rhythmically, moving the organism, and are made of nine double strands of microtubules and a central pair. According to Sloboda, similar IFT phenomena also take place in rod and cone cells of the human retina, in human kidney cells, and in nerve cells.

To determine where EB1 occurs in Chlamydomonas cells, the researchers cloned and sequenced the protein to make antibodies specific for EB1. The researchers found that the antibodies bound to the flagella tips, indicating that EB1 stays at the tip, and does not move along the length of the flagella.

“This unexpected observation led to the paper being featured on the cover of the journal,” says Sloboda. “It was a great result, because now we know more about the structure of the flagellar tip due to the presence of EB1. Using EB1 as bait, we can move on to fish out other proteins that associate with EB1 and learn how together these proteins are involved in tip structure and function and the process of IFT. Hopefully, our work will inform others working on colon cancer, kidney disease, vision, and central nervous system disorders such as Alzheimer’s and Lou Gehrig’s diseases.”

The other authors on the paper include Lotte Pedersen, a postdoctoral fellow at Yale University; Stefan Geimer, then a postdoctoral fellow at Yale University and now at the Institut Universität zu Köln in Cologne, Germany; and Joel Rosenbaum, Professor of Molecular, Cellular, and Developmental Biology at Yale University.

The study was funded by the National Institutes of Health, a fellowship from the Deutsche Forschungsgemeinschaft, and the Ira Allen Eastman (Class of 1829) Professorship at Dartmouth, which was established in 1910 through a gift to the College by his widow, Jane Eastman.