Abstract
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. Experiments have identified motor-driven transport of tubulin to the flagella tips as a key component of their length control. 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. 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. Next, we consider an extension of the limiting-pool model that incorporates proteins that depolymerize microtubules. 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.
Highlights
The size regulation of cellular organelles is a fundamental problem in biology (Marshall, 2016; Milo and Phillips, 2015)
We capture the aspects of intraflagellar transport (IFT) essential for length control, that is the motor-driven transport of tubulin across the flagellum, to explore models of flagellar length dynamics
In which we take the disassembly rate to be constant, we find that sharing both tubulin and motors leads to an indeterminate system of equations regardless of the details of the model, whereas sharing either tubulin or motors, but not both, results in simultaneous length control of both flagella
Summary
The size regulation of cellular organelles is a fundamental problem in biology (Marshall, 2016; Milo and Phillips, 2015). 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) 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)
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