Intraflagellar transport particle size scales inversely with flagellar length: revisiting the balance-point length control model

Engel, Benjamin D.; Ludington, William B.; Marshall, Wallace F.

doi:10.1083/jcb.200812084

Cited by 204 publications

(353 citation statements)

References 57 publications

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“…We used total internal reflection fluorescence (TIRF) microscopy of green fluorescent protein (GFP)-tagged IFT proteins in Chlamydomonas reinhardtii flagella (6,20) because of the availability of genetic mutants with abnormal flagellar length and the ease of flagellar imaging in this system (Fig. 1A).…”

Section: Resultsmentioning

confidence: 99%

Avalanche-like behavior in ciliary import

Ludington

Wemmer

Lechtreck

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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201

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Cilia and flagella are microtubule-based organelles that protrude from the cell body. Ciliary assembly requires intraflagellar transport (IFT), a motile system that delivers cargo from the cell body to the flagellar tip for assembly. The process controlling injections of IFT proteins into the flagellar compartment is, therefore, crucial to ciliogenesis. Extensive biochemical and genetic analyses have determined the molecular machinery of IFT, but these studies do not explain what regulates IFT injection rate. Here, we provide evidence that IFT injections result from avalanche-like releases of accumulated IFT material at the flagellar base and that the key regulated feature of length control is the recruitment of IFT material to the flagellar base. We used total internal reflection fluorescence microscopy of IFT proteins in live cells to quantify the size and frequency of injections over time. The injection dynamics reveal a power-law tailed distribution of injection event sizes and a negative correlation between injection size and frequency, as well as rich behaviors such as quasiperiodicity, bursting, and long-memory effects tied to the size of the localized load of IFT material awaiting injection at the flagellar base, collectively indicating that IFT injection dynamics result from avalanche-like behavior. Computational models based on avalanching recapitulate observed IFT dynamics, and we further show that the flagellar Ras-related nuclear protein (Ran) guanosine 5'-triphosphate (GTP) gradient can in theory act as a flagellar length sensor to regulate this localized accumulation of IFT. These results demonstrate that a self-organizing, physical mechanism can control a biochemically complex intracellular transport pathway.Chlamydomonas | self-organization | nuclear import | long flagella mutants | power spectrum C ilia and flagella generate fluid flows and mediate cell signaling (1), and ciliary length defects cause a wide range of congenital human diseases. Many of these defects arise from mutations in intraflagellar transport (IFT) proteins, which are required to build and maintain the length of cilia and flagella (2). The IFT proteins form complexes called IFT trains that haul cargo to the ciliary tip for assembly (3-7). IFT trains first localize to the basal body (8) and then enter the cilium as a group in an injection event. Understanding the IFT injection process is critical to understanding ciliary length control because the injection rate sets the overall amount of transport that in turn determines the rate of steadystate flagellar assembly (9).A previous report indicated that entry of new IFT trains is periodic (10), suggesting that a biochemical oscillator may regulate IFT injection. However, the biochemical components of this hypothetical oscillator are currently unknown. Components of the gate controlling entry into the cilium are being identified (4, 5), but identifying the oscillating components themselves could be an extremely difficult biochemical problem because it is not obvious how to determ...

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Section: Resultsmentioning

confidence: 99%

Avalanche-like behavior in ciliary import

Ludington

Wemmer

Lechtreck

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

118

201

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“…Toutefois, la quantité de tubuline fournie serait dépendante de la longueur [24]. La kinésine est alors inactivée et revient vers la base soit sous forme de cargo [15], soit par diffusion [30]. KAP : kinesin accessory protein ; DIC5 : chaîne intermédiaire de dynéine ; DLIC1 : chaîne légère intermédiaire de dynéine ; DHC2.1 : chaîne lourde de dynéine 2.…”

Section: Modèle 1 : Régulation Par L'équilibre Entre Assemblage Et Déunclassified

“…au cours du temps, ce qui a été démontré chez des souches de Chlamydomonas exprimant des protéines de fusion entre la GFP et des protéines de l'IFT [30]. Aux stades précoces, les trains expriment une fluorescence importante ; ils seraient plus gros et, de ce fait, transporteraient plus de tubuline ( Figure 5A).…”

Section: Revuesunclassified

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Élongation de l’axonème et dynamique du transport intraflagellaire

Fort

Bastin

2014

Med Sci (Paris)

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“…The decrease in ciliary length due to fluid flow was found to require the polycystins PC1 (also known as PKD1) and PC2 and downstream signaling mediated by Ca 2+ signaling pathways (Besschetnova et al 2010). These researchers also reported a decrease in intraflagellar transport speed, but it is not clear whether this is a cause of the ciliary shortening or a consequence, because the speed of the IFT particles is known to be a function of length (Engel et al 2009). …”

Section: Mechanical Forces Affect Ciliogenesismentioning

confidence: 99%

Mechanobiology of Ciliogenesis

Ishikawa¹,

Marshall²

2014

BioScience

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Cilia are force-generating and -sensing organelles that serve as mechanical interfaces between the cell and the extracellular environment. Cilia are present in tissues that adaptively respond to mechanical loading and fluid flow, and defects in ciliary function can lead to diseases affecting these tissues. As might be expected for a mechanical interface, the formation of cilia is, itself, regulated by mechanical forces, and these links between mechanics and ciliary formation are providing new entry points for dissecting the regulatory pathways of ciliogenesis.

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Intraflagellar transport particle size scales inversely with flagellar length: revisiting the balance-point length control model

Abstract: Chlamydomonas reinhardtii IFT particle trains, important for flagella maintenance and assembly, are observed to decrease in size as a function of cilia length.

Cited by 204 publications

References 57 publications

Avalanche-like behavior in ciliary import

Avalanche-like behavior in ciliary import

Élongation de l’axonème et dynamique du transport intraflagellaire

Mechanobiology of Ciliogenesis

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