Intraflagellar Transport

Scholey, Jonathan M.

doi:10.1146/annurev.cellbio.19.111401.091318

Cited by 383 publications

(389 citation statements)

References 101 publications

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“…Just over a decade ago, Joel Rosenbaum and his colleagues discovered particles rapidly (2-4 mm/s) moving up and down within the flagella of Chlamydomonas 22 in a process they named intraflagellar transport (IFT; for recent reviews, see Rosenbaum and Witman 20 and Scholey 23 ). Since then, in a flurry of activity, cell biologists have built upon this original observation to arrive at the current model for the mechanism of assembly of cilia.…”

Section: Assembling a Cilium: The Intraflagellar Transport Machinerymentioning

confidence: 99%

Cilium-generated signaling and cilia-related disorders

Pan

Wang

Snell

2005

Laboratory Investigation

210

183

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Biologists have long known that humans experience their environment through cilia. Light, odorant, and sound perception depend on these microtubule-filled, complex organelles present on cells in primary sensory tissues. Recently, discoveries on the mechanism of assembly of cilia (flagella) in the lowly, biflagellated, eucaryotic green alga Chlamydomonas have triggered a renaissance of interest in the organelles along with a recognition of their key sensory roles in nonsensory tissues. Chlamydomonas researchers uncovered an entirely new set of cellular machinery essential for transporting the protein components of cilia and flagella in all ciliated/ flagellated eukaryotic cells between their site of synthesis in the cell body and their site of assembly at the tip of the flagellum (intraflagellar transport: IFT). Prompted by the surprising observations that disruption of IFT genes in mice led to polycystic kidney disease (PKD) and that PKD proteins are present on the sensory cilia of Caenorhabditis elegans, researchers have made a direct connection between PKD and cilia. At least five (and possibly all) of the seven identified human genes disrupted in PKD and a related disorder nephronophthisis encode proteins expressed in the primary cilia that project into the lumen from the epithelial cells that line renal tubules. Moreover, the renal cilia are flow sensors and at least two of the PKD genes encode ciliary transmembrane proteins essential for mechanosensation. Although their roles have not yet been as clearly identified, cilia also are at the center of a rare human disorder, Bardet-Biedl syndrome (BBS), in which patients exhibit phenotypes of common human diseases, including obesity and increased incidence of hypertension and diabetes. Five of the eight known BBS genes encode basal body or cilia proteins in mice or humans, and homologues of two of the remaining genes are present in basal bodies/cilia of model organisms. Here we briefly describe the biology of cilia and flagella, we outline how studies on model organisms have led to our current understanding of the roles of these organelles and their proteins in health and disease, and we highlight the notion that the primary cilia present on cells throughout the body, even those on brain neurons, may be essential for as yet undiscovered cilium-generated signaling functions.

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Section: Assembling a Cilium: The Intraflagellar Transport Machinerymentioning

confidence: 99%

Cilium-generated signaling and cilia-related disorders

Pan

Wang

Snell

2005

Laboratory Investigation

210

183

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“…Cilium biogenesis and maintenance depend on a microtuble associated transport machinery: intraflagellar transport (IFT) (Kozminski et al 1993;Rosenbaum & Witman 2002;Scholey 2003). The IFT machinery conveys cargo, such as receptors and channels, to the ciliary tip by kinesin-II motors and recycles components to the basal body by a dynein motor (Rosenbaum & Witman 2002;Cole 2003;Scholey 2003;Inglis et al 2006).…”

Section: Introductionmentioning

confidence: 99%

“…The IFT machinery conveys cargo, such as receptors and channels, to the ciliary tip by kinesin-II motors and recycles components to the basal body by a dynein motor (Rosenbaum & Witman 2002;Cole 2003;Scholey 2003;Inglis et al 2006). The motors cooperate with a multiprotein complex, IFT particle, which consists of two subcomplexes, A and B (Piperno & Mead 1997;Cole et al 1998).…”

Section: Introductionmentioning

confidence: 99%

IFT‐81 and IFT‐74 are required for intraflagellar transport in C. elegans

Kobayashi¹,

Gengyo-Ando²,

Ishihara³

et al. 2007

Genes to Cells

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“…The size of an organelle is determined by the balance between assembly pathways that deliver structural components and disassembly pathways that remove components. In cilia, the intraflagellar transport (IFT), a bidirectional motility system that operates inside cilia (Rosenbaum and Witman, 2002;Scholey, 2003), plays a key role in length regulation. The anterograde IFT supplies structural subunits during assembly (Piperno et al, 1996;Qin et al, 2005) and maintains the axoneme after assembly (Brown et al, 1999).…”

mentioning

confidence: 99%

Members of the NIMA-related Kinase Family Promote Disassembly of Cilia by Multiple Mechanisms

Włoga

Camba

Rogowski

et al. 2006

MBoC

104

103

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The genome of Tetrahymena thermophila contains 39 loci encoding NIMA-related kinases (NRKs), an extraordinarily large number for a unicellular organism. Evolutionary analyses grouped these sequences into several subfamilies, some of which have orthologues in animals, whereas others are protist specific. When overproduced, NRKs of three subfamilies caused rapid shortening of cilia. Ultrastructural studies revealed that each NRK triggered ciliary resorption by a distinct mechanism that involved preferential depolymerization of a subset of axonemal microtubules, at either the distal or proximal end. Overexpression of a kinase-inactive variant caused lengthening of cilia, indicating that constitutive NRK-mediated resorption regulates the length of cilia. Each NRK preferentially resorbed a distinct subset of cilia, depending on the location along the anteroposterior axis. We also show that normal Tetrahymena cells maintain unequal length cilia. We propose that ciliates used a large number of NRK paralogues to differentially regulate the length of specific subsets of cilia in the same cell. INTRODUCTIONHow the size of organelles is determined is an important and largely unanswered question. Cilia have emerged as a model organelle to study the mechanism of size regulation (Marshall, 2002). The size of an organelle is determined by the balance between assembly pathways that deliver structural components and disassembly pathways that remove components. In cilia, the intraflagellar transport (IFT), a bidirectional motility system that operates inside cilia (Rosenbaum and Witman, 2002;Scholey, 2003), plays a key role in length regulation. The anterograde IFT supplies structural subunits during assembly (Piperno et al., 1996;Qin et al., 2005) and maintains the axoneme after assembly (Brown et al., 1999). The retrograde IFT recycles the IFT machinery (Signor et al., 1999) and removes ciliary structural components that turn over (Qin et al., 2004). This turnover is the basis of the disassembly pathway (Stephens, 1997;Marshall and Rosenbaum, 2001;Song and Dentler, 2001;Thazhath et al., 2004). Experimental data and mathematical modeling in Chlamydomonas reinhardtii indicate that the length of flagella is dependent on the rates of elongation (equivalent to the efficiency of anterograde IFT) and disassembly. As the flagellum grows, the rate of elongation decreases due to the limited supply of IFT components that need to travel longer distances to the tip (Marshall and Rosenbaum, 2001). According to the "balance point model," the steady-state length is achieved when the rate of elongation equals the rate of disassembly (Marshall and Rosenbaum, 2001;Marshall et al., 2005).The length of already assembled cilia can be reduced drastically using two mechanisms: autotomy or resorption (reviewed by Quarmby, 2004). During autotomy, the axoneme breaks off from the basal body, the cilium falls off, and the plasma membrane reseals over the basal body. Protists undergo autotomy in response to low pH (Lewin et al., 1982). It is unclear whether...

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Intraflagellar Transport

Cited by 383 publications

References 101 publications

Cilium-generated signaling and cilia-related disorders

Cilium-generated signaling and cilia-related disorders

IFT‐81 and IFT‐74 are required for intraflagellar transport in C. elegans

Members of the NIMA-related Kinase Family Promote Disassembly of Cilia by Multiple Mechanisms

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