Functional coordination of intraflagellar transport motors

Guangshuo Ou, Oliver E. Blacque, Joshua J. Snow, Michel R. Leroux, Jonathan M. Scholey

Research output: Contribution to journalArticle

259 Citations (Scopus)

Abstract

Cilia have diverse roles in motility and sensory reception, and defects in cilia function contribute to ciliary diseases such as Bardet-Biedl syndrome (BBS). Intraflagellar transport (IFT) motors assemble and maintain cilia by transporting ciliary precursors, bound to protein complexes called IFT particles, from the base of the cilium to their site of incorporation at the distal tip. In Caenorhabditis elegans, this is accomplished by two IFT motors, kinesin-II and osmotic avoidance defective (OSM)-3 kinesin, which cooperate to form two sequential anterograde IFT pathways that build distinct parts of cilia. By observing the movement of fluorescent IFT motors and IFT particles along the cilia of numerous ciliary mutants, we identified three genes whose protein products mediate the functional coordination of these motors. The BBS proteins BBS-7 and BBS-8 are required to stabilize complexes of IFT particles containing both of the IFT motors, because IFT particles in bbs-7 and bbs-8 mutants break down into two subcomplexes, IFT-A and IFT-B, which are moved separately by kinesin-II and OSM-3 kinesin, respectively. A conserved ciliary protein, DYF-1, is specifically required for OSM-3 kinesin to dock onto and move IFT particles, because OSM-3 kinesin is inactive and intact IFT particles are moved by kinesin-II alone in dyf-1 mutants. These findings implicate BBS ciliary disease proteins and an OSM-3 kinesin activator in the formation of two IFT pathways that build functional cilia.

Original languageEnglish (US)
Pages (from-to)583-587
Number of pages5
JournalNature
Volume436
Issue number7050
DOIs
StatePublished - Jul 28 2005

Fingerprint

Cilia
Kinesin
Bardet-Biedl Syndrome
Proteins
Caenorhabditis elegans
kinesin-II

ASJC Scopus subject areas

  • General

Cite this

Ou, G., Blacque, O. E., Snow, J. J., Leroux, M. R., & Scholey, J. M. (2005). Functional coordination of intraflagellar transport motors. Nature, 436(7050), 583-587. https://doi.org/10.1038/nature03818

Functional coordination of intraflagellar transport motors. / Ou, Guangshuo; Blacque, Oliver E.; Snow, Joshua J.; Leroux, Michel R.; Scholey, Jonathan M.

In: Nature, Vol. 436, No. 7050, 28.07.2005, p. 583-587.

Research output: Contribution to journalArticle

Ou, G, Blacque, OE, Snow, JJ, Leroux, MR & Scholey, JM 2005, 'Functional coordination of intraflagellar transport motors', Nature, vol. 436, no. 7050, pp. 583-587. https://doi.org/10.1038/nature03818
Ou G, Blacque OE, Snow JJ, Leroux MR, Scholey JM. Functional coordination of intraflagellar transport motors. Nature. 2005 Jul 28;436(7050):583-587. https://doi.org/10.1038/nature03818
Ou, Guangshuo ; Blacque, Oliver E. ; Snow, Joshua J. ; Leroux, Michel R. ; Scholey, Jonathan M. / Functional coordination of intraflagellar transport motors. In: Nature. 2005 ; Vol. 436, No. 7050. pp. 583-587.
@article{0761494a42ad4830a42cbced68717c21,
title = "Functional coordination of intraflagellar transport motors",
abstract = "Cilia have diverse roles in motility and sensory reception, and defects in cilia function contribute to ciliary diseases such as Bardet-Biedl syndrome (BBS). Intraflagellar transport (IFT) motors assemble and maintain cilia by transporting ciliary precursors, bound to protein complexes called IFT particles, from the base of the cilium to their site of incorporation at the distal tip. In Caenorhabditis elegans, this is accomplished by two IFT motors, kinesin-II and osmotic avoidance defective (OSM)-3 kinesin, which cooperate to form two sequential anterograde IFT pathways that build distinct parts of cilia. By observing the movement of fluorescent IFT motors and IFT particles along the cilia of numerous ciliary mutants, we identified three genes whose protein products mediate the functional coordination of these motors. The BBS proteins BBS-7 and BBS-8 are required to stabilize complexes of IFT particles containing both of the IFT motors, because IFT particles in bbs-7 and bbs-8 mutants break down into two subcomplexes, IFT-A and IFT-B, which are moved separately by kinesin-II and OSM-3 kinesin, respectively. A conserved ciliary protein, DYF-1, is specifically required for OSM-3 kinesin to dock onto and move IFT particles, because OSM-3 kinesin is inactive and intact IFT particles are moved by kinesin-II alone in dyf-1 mutants. These findings implicate BBS ciliary disease proteins and an OSM-3 kinesin activator in the formation of two IFT pathways that build functional cilia.",
author = "Guangshuo Ou and Blacque, {Oliver E.} and Snow, {Joshua J.} and Leroux, {Michel R.} and Scholey, {Jonathan M.}",
year = "2005",
month = "7",
day = "28",
doi = "10.1038/nature03818",
language = "English (US)",
volume = "436",
pages = "583--587",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7050",

}

TY - JOUR

T1 - Functional coordination of intraflagellar transport motors

AU - Ou, Guangshuo

AU - Blacque, Oliver E.

AU - Snow, Joshua J.

AU - Leroux, Michel R.

AU - Scholey, Jonathan M.

PY - 2005/7/28

Y1 - 2005/7/28

N2 - Cilia have diverse roles in motility and sensory reception, and defects in cilia function contribute to ciliary diseases such as Bardet-Biedl syndrome (BBS). Intraflagellar transport (IFT) motors assemble and maintain cilia by transporting ciliary precursors, bound to protein complexes called IFT particles, from the base of the cilium to their site of incorporation at the distal tip. In Caenorhabditis elegans, this is accomplished by two IFT motors, kinesin-II and osmotic avoidance defective (OSM)-3 kinesin, which cooperate to form two sequential anterograde IFT pathways that build distinct parts of cilia. By observing the movement of fluorescent IFT motors and IFT particles along the cilia of numerous ciliary mutants, we identified three genes whose protein products mediate the functional coordination of these motors. The BBS proteins BBS-7 and BBS-8 are required to stabilize complexes of IFT particles containing both of the IFT motors, because IFT particles in bbs-7 and bbs-8 mutants break down into two subcomplexes, IFT-A and IFT-B, which are moved separately by kinesin-II and OSM-3 kinesin, respectively. A conserved ciliary protein, DYF-1, is specifically required for OSM-3 kinesin to dock onto and move IFT particles, because OSM-3 kinesin is inactive and intact IFT particles are moved by kinesin-II alone in dyf-1 mutants. These findings implicate BBS ciliary disease proteins and an OSM-3 kinesin activator in the formation of two IFT pathways that build functional cilia.

AB - Cilia have diverse roles in motility and sensory reception, and defects in cilia function contribute to ciliary diseases such as Bardet-Biedl syndrome (BBS). Intraflagellar transport (IFT) motors assemble and maintain cilia by transporting ciliary precursors, bound to protein complexes called IFT particles, from the base of the cilium to their site of incorporation at the distal tip. In Caenorhabditis elegans, this is accomplished by two IFT motors, kinesin-II and osmotic avoidance defective (OSM)-3 kinesin, which cooperate to form two sequential anterograde IFT pathways that build distinct parts of cilia. By observing the movement of fluorescent IFT motors and IFT particles along the cilia of numerous ciliary mutants, we identified three genes whose protein products mediate the functional coordination of these motors. The BBS proteins BBS-7 and BBS-8 are required to stabilize complexes of IFT particles containing both of the IFT motors, because IFT particles in bbs-7 and bbs-8 mutants break down into two subcomplexes, IFT-A and IFT-B, which are moved separately by kinesin-II and OSM-3 kinesin, respectively. A conserved ciliary protein, DYF-1, is specifically required for OSM-3 kinesin to dock onto and move IFT particles, because OSM-3 kinesin is inactive and intact IFT particles are moved by kinesin-II alone in dyf-1 mutants. These findings implicate BBS ciliary disease proteins and an OSM-3 kinesin activator in the formation of two IFT pathways that build functional cilia.

UR - http://www.scopus.com/inward/record.url?scp=23144445446&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23144445446&partnerID=8YFLogxK

U2 - 10.1038/nature03818

DO - 10.1038/nature03818

M3 - Article

VL - 436

SP - 583

EP - 587

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7050

ER -