Sensory ciliogenesis in Caenorhabditis elegans:: Assignment of IFT components into distinct modules based on transport and phenotypic profiles

被引:107
作者
Ou, Guangshuo
Koga, Makato
Blacque, Oliver E.
Murayama, Takashi
Ohshima, Yasumi
Schafer, Jenny C.
Li, Chunmei
Yoder, Bradley K.
Leroux, Michel R. [1 ]
Scholey, Jonathan M.
机构
[1] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada
[2] Univ Calif Davis, Ctr Genet & Dev, Sect Mol & Cellular Biol, Davis, CA 95616 USA
[3] Kyushu Univ, Fac Sci, Dept Biol, Grad Sch, Fukuoka 8128581, Japan
[4] Univ Coll Dublin, Sch Biomol & Biomed Sci, Dublin Conway Inst, Dublin 4, Ireland
[5] Univ Alabama Birmingham, Dept Cell Biol, Birmingham, AL 35294 USA
关键词
D O I
10.1091/mbc.E06-09-0805
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Sensory cilium biogenesis within Caenorhabditis elegans neurons depends on the kinesin-2-dependent intraflagellar transport (IFT) of ciliary precursors associated with IFT particles to the axoneme tip. Here we analyzed the molecular organization of the IFT machinery by comparing the in vivo transport and phenotypic profiles of multiple proteins involved in IFT and ciliogenesis. Based on their motility in wild-type and bbs (Bardet-Biedl syndrome) mutants, IFT proteins were classified into groups with similar transport profiles that we refer to as "modules." We also analyzed the distribution and transport of fluorescent IFT particles in multiple known ciliary mutants and 49 new ciliary mutants. Most of the latter mutants were snip-SNP mapped and one, namely dyf-14(ks69), was cloned and found to encode a conserved protein essential for ciliogenesis. The products of these ciliogenesis genes could also be assigned to the aforementioned set of modules or to specific aspects of ciliogenesis, based on IFT particle dynamics and ciliary mutant phenotypes. Although binding assays would be required to confirm direct physical interactions, the results are consistent with the hypothesis that the C. elegans IFT machinery has a modular design, consisting of modules IFT-subcomplex A, IFT-subcomplex B, and a BBS protein complex, in addition to motor and cargo modules, with each module contributing to distinct functional aspects of IFT or ciliogenesis.
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页码:1554 / 1569
页数:16
相关论文
共 71 条
[1]   Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome [J].
Ansley, SJ ;
Badano, JL ;
Blacque, OE ;
Hill, J ;
Hoskins, BE ;
Leitch, CC ;
Kim, JC ;
Ross, AJ ;
Eichers, ER ;
Teslovich, TM ;
Mah, AK ;
Johnsen, RC ;
Cavender, JC ;
Lewis, RA ;
Leroux, MR ;
Beales, PL ;
Katsanis, N .
NATURE, 2003, 425 (6958) :628-633
[2]   Decoding cilia function: Defining specialized genes required for compartmentalized cilia biogenesis [J].
Avidor-Reiss, T ;
Maer, AM ;
Koundakjian, E ;
Polyanovsky, A ;
Keil, T ;
Subramaniam, S ;
Zuker, CS .
CELL, 2004, 117 (04) :527-539
[3]   The ciliopathies: An emerging class of human genetic disorders [J].
Badano, Jose L. ;
Mitsuma, Norimasa ;
Beales, Phil L. ;
Katsanis, Nicholas .
ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, 2006, 7 :125-148
[4]   IFT20 links kinesin II with a mammalian intraflagellar transport complex that is conserved in motile flagella and sensory cilia [J].
Baker, SA ;
Freeman, K ;
Luby-Phelps, K ;
Pazour, GJ ;
Besharse, JC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (36) :34211-34218
[5]  
BARGMANN CI, 1997, C ELEGANS, V2, P717
[6]   The molecular identities of the Caenorhabditis elegans intraflagellar transport genes dyf-6, daf-10 and osm-1 [J].
Bell, Leslie R. ;
Stone, Steven ;
Yochem, John ;
Shaw, Jocelyn E. ;
Herman, Robert K. .
GENETICS, 2006, 173 (03) :1275-1286
[7]   Bardet-Biedl syndrome: an emerging pathomechanism of intracellular transport [J].
Blacque, O. E. ;
Leroux, M. R. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2006, 63 (18) :2145-2161
[8]   Loss of C-elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport [J].
Blacque, OE ;
Reardon, MJ ;
Li, CM ;
McCarthy, J ;
Mahjoub, MR ;
Ansley, SJ ;
Badano, LL ;
Mah, AK ;
Beales, PL ;
Davidson, WS ;
Johnsen, RC ;
Audeh, M ;
Plasterk, RHA ;
Baillie, DL ;
Katsanis, N ;
Quarmby, LM ;
Wicks, SR ;
Leroux, MR .
GENES & DEVELOPMENT, 2004, 18 (13) :1630-1642
[9]   Functional genomics of the cilium, a sensory organelle [J].
Blacque, OE ;
Perens, EA ;
Boroevich, KA ;
Inglis, PN ;
Li, CM ;
Warner, A ;
Khattra, J ;
Holt, RA ;
Ou, GS ;
Mah, AK ;
McKay, SJ ;
Huang, P ;
Swoboda, P ;
Jones, SJM ;
Marra, MA ;
Baillie, DL ;
Moerman, DG ;
Shaham, S ;
Leroux, MR .
CURRENT BIOLOGY, 2005, 15 (10) :935-941
[10]   The WD repeat-containing protein IFTA-1 is required for retrograde intraflagellar transport [J].
Blacque, Oliver E. ;
Li, Chunmei ;
Inglis, Peter N. ;
Esmail, Muneer A. ;
Ou, Guangshuo ;
Mah, Allan K. ;
Baillie, David L. ;
Scholey, Jonathan M. ;
Leroux, Michel R. .
MOLECULAR BIOLOGY OF THE CELL, 2006, 17 (12) :5053-5062