IFT particles containing tubulin are transported along the flagellum by two different motor proteins: kinesin-2 transports IFT particles from the flagellar base to tip (the anterograde direction) whereas dynein carries IFT particles from the tip to the base (the retrograde direction). elegans, as described in several review articles ( Prevo et al., 2017 Scholey, 2003 Scholey, 2008 Cole, 2003 Rosenbaum et al., 1999 Rosenbaum and Witman, 2002 Rosenbaum et al., 1999).Īlready at the time of its discovery, IFT was hypothesized to play a role in flagellar length control by transporting building blocks to the tip of the flagellum ( Kozminski et al., 1993). In the time since, a significant body of work has revealed the many proteins and biochemical pathways that coordinate this complex process in Chlamydomonas and other organisms such as C. The original evidence for this intraflagellar transport (IFT) was provided around 25 years ago by experimental observations in Chlamydomonas of particles moving processively along the flagellum at constant speed ( Kozminski et al., 1993). The green and blue shaded regions show the mean plus or minus one standard deviation.Ī key process contributing to the assembly of flagella is the continual transport of proteins from the flagellar base to tip and back. This is demonstrated in experimental data of 20 severing experiments from Ludington et al. ( b) Severing experiments: after one flagellum is severed, the two flagella equalize at a shorter length and then grow together to the original steady-state length. ( a) Electron microscopy images of the biflagellate green algae Chlamydomonas and its flagella captured by Elisa Vannuccini and Pietro Lupetti (University of Siena, Italy) and reproduced from Morga and Bastin (2013) under the Creative Commons Attribution License CC BY 2.0 ). The inset shows the whole organism (scale bar 5 µm) and the close-up shows the flagellar basal body (BB), transition zone (TZ), and cell wall (CW) (scale bar 1 µm). This stability reflects a tight control over flagellar lengths, the loss of which has dramatic physiological consequences mutants with longer flagella have decreased swimming velocities and beat frequencies ( Khona et al., 2013) compared to wild type cells and mutants with unequal flagellar lengths are observed to spin around in circles ( Tam et al., 2003). Unlike the dynamic instability of cytoplasmic microtubules, which can alternate between rapidly shortening ‘catastrophe’ and stable ‘rescue’ states depending on whether or not the tip is bound to GTP, microtubules in the axoneme exist in a highly stable state ( Behnke and Forer, 1967 Orbach and Howard, 2019). The backbone of each flagellum is an assembly known as the axoneme that consists of nine microtubule doublets arranged in a ring around a central pair of microtubules ( Fawcett and Porter, 1954 Witman et al., 1972). For example, nuclear size is tightly coupled with cell size across a wide range of species ( Hara and Merten, 2015) and the loss of this coupling mechanism is implicated in various types of cancer ( Zink et al., 2004).Ī striking example of organelle size control in eukaryotes is the single-celled algae Chlamydomonas reinhardtii ( Figure 1), which uses two flagella to move through its aqueous environment. The size regulation of cellular organelles is a fundamental problem in biology ( Marshall, 2016 Milo and Phillips, 2015). We show that this ‘active disassembly’ model of flagellar length control explains in quantitative detail the results of severing experiments and use it to make predictions that can be tested in experiments. Next, we consider an extension of the limiting-pool model that incorporates proteins that depolymerize microtubules. We show that the limiting-pool assumption is insufficient to describe the results of severing experiments, in which a flagellum is regenerated after it has been severed. Here we consider a class of models whose key assumption is that proteins responsible for the intraflagellar transport (IFT) of tubulin are present in limiting amounts. Experiments have identified motor-driven transport of tubulin to the flagella tips as a key component of their length control. The single-celled green algae Chlamydomonas reinhardtii with its two flagella-microtubule-based structures of equal and constant lengths-is the canonical model organism for studying size control of organelles.
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