Overview Of Eukaryotic Flagella From A Mechanistic Perspective

Eukaryotic flagella are bending machines to drive cells forward or backward with chemical energy by hydrolyzing ATP (adenosine 3-phosphate). They have 5~10 micron length and 0.3 micron diameter and flagella from various species share the identical structure (“9+2”), where nine microtubule (cytoskeletal proteins) doublets surround two microtubule singlets. Although flagella consist of more than 200 proteins totally, it is known that the driving force is generated by ATP-driven motor proteins called dynein. In flagella, dynein molecules bridge two adjacent microtubule doublets and cause sliding motion. Our questions are (1) how this sliding motion is generated and (2) how the sliding motion between dynein and microtubules are integrated into a flagellar bending motion. We are trying to reveal these mechanisms by structural study using electron microscopy and image analysis.

Dynein molecules form two gigantic complexes on microtubule doublets: inner- and outer-dynein arms. According to physiological studies using light microscopy, the inner dynein arm determines the waveform of flagella, whereas the outer dynein arm is an accelerator. Biochemistry and molecular biology proved that the main components of these dynein arms are so-called heavy chains. Each heavy chain has ~500,000 molecular weight with a ring-shaped head, a coiled-coil stalk and a long tail. On microtubule doublets, the outer dynein arm is located with 24nm periodicity with three heavy chains, while the inner dynein arm has 96nm periodicity and eight heavy chains. Using a new technique of electron microscopy called cryo-electron tomography, we proved that three heavy chains stack together like three coins in the outer-dynein arm and two adjacent outer dynein arms are connected by two linkers (Ishikawa et al. (2007) J. Mol. Biol. 368, 1249). On the contrary, eight heavy chains in the inner dynein arms are arranged horizontally to make an array (Bui et al., manuscript in preparation). In this talk, I will overview the physiological, biochemical and structural knowledge on eukaryotic flagella and discuss their function as bending nano-machines.

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