Intraflagellar transport

Nature Reviews Molecular Cell Biology

Volumn 3, Issue 11, 2002, Pages 813-825

  Rosenbaum, Joel L ^a   Witman, George B ^b  

^a YALE UNIVERSITY   (United States)

^b UNIVERSITY OF MASSACHUSETTS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARRIER PROTEIN; INTRAFLAGELLAR TRANSPORT PROTEIN; MEMBRANE PROTEIN; POLYCYSTIN; UNCLASSIFIED DRUG;

BARDET BIEDL SYNDROME; CAENORHABDITIS ELEGANS; CHLAMYDOMONAS REINHARDTII; CILIARY MOTILITY; CORRELATION ANALYSIS; EMBRYO DEVELOPMENT; EUKARYOTE; FLAGELLUM; GENE FUNCTION; GENE MUTATION; HUMAN; KIDNEY POLYCYSTIC DISEASE; NONHUMAN; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; RETINA DEGENERATION; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ANALYSIS;

ANIMALS; BIOLOGICAL TRANSPORT; CILIA; FLAGELLA; HUMANS; POLYCYSTIC KIDNEY DISEASES; RETINAL DEGENERATION; SIGNAL TRANSDUCTION;

CAENORHABDITIS; CAENORHABDITIS ELEGANS; CHLAMYDOMONAS; CHLAMYDOMONAS REINHARDTII; EUKARYOTA;

EID: 0036844195     PISSN: 14710072     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrm952     Document Type: Review

References (104)

1. Rosenbaum, J. L. & Child, F. M. Flagellar regeneration in protozoan flagellates. J. Cell Biol. 34, 345-364 (1967).
2. Binder, L. I., Dentler, W. L. & Rosenbaum J. L. Assembly of chick brain tubulin onto flagellar microtubules from Chlamydomonas and sea urchin sperm. Proc. Natl. Acad. Sci. USA 72, 1122-1126 (1975).
3. Witman, G. B. The site of in vivo assembly of flagellar microtubules. Ann. NY Acad. Sci. 253, 178-19t (1975).
4. Johnson, K. A. & Rosenbaum, J. L. Polarity of flagellar assembly in Chlamydomonas. J. Cell Biol. 119, 1605-1611(1992).
5. Piperno, G., Mead. K. & Henderson, S. Inner dynein arms but not outer dynein arms require the activity of kinesin homologue protein KHP1 to reach the distal part of the flagella in Chlamydomonas. J. Cell Biol. 133, 371-379(1996). This paper showed that the IFT anterograde motor kinesin-II is required for transport of inner dynein arms to their site of assembly in the flagellum, This was the first identification of an IFT cargo.
6. Kozminski, K. G., Beech, P. L. & Rosenbaum, J. L. The Chlamydomonas kinesin-like protein FLA10 is involved in motility associated with the flagellar membrane. J. Cell Biol. 131, 1517-1527 (1995). This study unequivocally correlated the IFT particles viewed by light microscopy with the linear arrays of particles seen by EM, and implicated the kinesin-like protein Fla1O in anterograde IFT.
7. Pazour, G. J., Dickert, B. L. & Witman, G. B. The DHC1b (DHC2) isoform of cytoplasmic dynein is required for flagellar assembly. J. Cell Biol. 144, 473-481 (1999).
8. Pazour, G. J. et al. Chlamydomonas IFT88 and its mouse homologue, polycyslic kidney disease gene Tg737, are required for assembly of cilia and flagella. J. Cell Biol. 151, 709-718 (2000). This work showed that the IFT-particle protein IFT88 and its mouse homologue Tg737 are necessary for assembly of Chlamydomonas flagella and mouse kidney primary cilia, respectively. This provided the first link between defects In kidney cilia and kidney disease.
9. Morris, R. L. & Scholey, J. M. Heterotrimeric kinesin-II is required for the assembly of motile 9+2 ciliary axonemes on sea urchin embryos. J. Cell Biol. 138, 1009-1022(1997).
10. Brown, J. M., Marsala, C., Kosoy, R. & Gaertig, J. Kinesin-II is preferentially targeted to assembling cilia and is required for ciliogenesis and normal cytokinesis in Tetrahymena. Mol Biol. Cell 10, 3081-3096 (1999).
11. Perkins, L. A., Hedgecock, E. M., Thomson, J. N. & Culotti, J. G. Mutant sensory cilia in the nematode Caenorhabditis elegans, Dev. Biol. 117, 456-487 (1986).
12. Cole, D. G. et al. Chlamydomonas kinesin II-dependent intraflagellar transport (IFT): IFT particles contain proteins required for ciliary assembly in Caenorhabditis elegans sensory neurons. J.Cell Biol. 141, 993-1008 (1998). This paper first reported the purification and subunit composition of the Chlamydomonas anterograde IFT motor FlalO-kinesin-II, and first identified homologues of the Chlamydomonas IFT-particle proteins in C. Elegans and mammals.
13. Collet, J., Spike, C. A., Lundquist, J. E, Shaw, J. E. & Herman, R. K. Analysis of osm-6, a gene that affects sensory cilium structure and sensory neuron function in Caenorhabditis elegans, Genetics 148, 187-200 (1998).
14. Signor, D. et al. Role of a class DHC1b dynein in retrograde transport of IFF motors and IFF raft particles along cilia, but not dendrites, in chemosensory neurons of living Caenorhabditis elegans. J.Cell Biol. 147. 519-530(1999).
15. Wicks, S. R., de Vries, C. J., van Luenen, H.G.A. M. & Plasterk, R. H. A. CHE-3, a cytosolic dynein heavy chain, is required for sensory cilia structure and function in Caenorhabditis elegans, Dev. Biol. 221, 295-307 (2000).
16. Qin, H., Rosenbaum, J. L. & Barr, M.M. An autosomal recessive polycystic kidney disease gene homolog is involved in intraflagellar transport in C. Elegans ciliated sensory neurons. Curr. Biol. 11, 1-20(2001).
17. Nonaka, S. ef al. Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell 95, 829-837 (1998). By knocking out a subunit of the anterograde IFT motor kinesin-II in the mouse, these authors showed that loss of nodal cilia caused situs inversus. This, and further work (references 18-20) led to the hypothesis that the nodal cilia set up a morphogenetic gradient that determines left-right asymmetry.
18. Marszalek, J. R., Ruiz-Lozano, P., Roberts, E., Chien, K. R. & Goldstein, L. S. Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-ll Proc. Natl. Acad. Sci. USA 96, 5043-5048(1999).
19. Takeda, S. et al. Left-right asymmetry and kinesin superfamily protein KIF3A: New insights in determination of laterality and mesoderm induction by kif3A mice analysis. J. Cell Biol. 145, 825-836 (1999).
20. Murcia, N.S. et al The oak ridge polycystic kidney(orpk) disease gene is required for leftright axis determination. Development 127, 2347-2355 (2000).
21. Marszalek, J. R. et al. Genetic evidence for selective transport of opsin and arrestin by kinesin.II in mammalian photoreceptors. Cell 102, 175-187 (2000). Using Cre-loxP mutagenesis, these investigators selectively removed a subunit of kinesin-ll from mouse photoreceptor cells. The results implicated kinesin-ll in protein transport through the cilium that connects the inner and outer segments.
22. Pazour, G. J. et al. The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance. J. Cell Biol. 157, 103-114 (2002). This work showed that a defect in the expression of an IFT-particle protein in the mouse photoreceptor cell leads to a slow degeneration of the retina similar to that seen in some human diseases.
23. Sloboda, R. D. A healthy understanding ofintraflagellar transport. Cell Motil. Cytoskeleton 52, 1-8 (2002).
24. Kozminski, K. G., Johnson, K. A., Forscher, P. & Rosenbaum, J. L. A motility in the eukaryotic flagellum unrelated to flagellar beating. Proc. Natl. Acad. Sci. USA 90, 5519-5523(1993). The first report of IFT. It showed the existence of IFT in Chlamydomonas, described the ultrastructure of the IFT particles and reported their rates of movement in both.the anterograde and retrograde directions.
25. Pazour, G. J., Wilkerson, C. G. & Witman, G. B. A dynein light chain is essential for the retrograde particle movement of intraflagellar transport (IFT). J. Cell Biol. 141, 979-992 (1998). This paper showed that a Chlamydomonas mutant lacking dynein light chain LC8 is defective in retrograde IFT. This set the stage for identification of cytoplasmic dynein lb as the retrograde motor (references 7, 41).
26. Orozco, J. T. et al. Movement of motor and cargo along cilia, Nature 398, 674 (1999). By using GFP to tag both the anterograde IFT motor kinesin-ll and the IFT-particle protein OSM-6 in C. Elegans, these investigators showed that both proteins moved anterogradely at the same rate in the worm's sensory cilia. This supported the hypothesis that kinesin-ll is the anterograde IFT motor.
27. Allen, C. & Borisy, G. G. Structural polarity and directional growth of microtubules of Chlamydomonas flagella. J. Mol. Biol. 90, 381-402 (1974).
28. Hirokawa, N. Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279, 519-526 (1998).
29. Huang, B., Rifkin, M. R. & Luck, D. J. Temperature-sensitive mutations affecting flagellar assembly and function in Chlamydomonas reinhardtii, J. Cell Biol. 72, 67-85(1977).
30. Adams, G. M. W., Huang, B. & Luck, D. J. L. Temperature-sensitive, assembly-defective flagella mutants of Chlamydomonas reinhardtii. Genetics 100, 579-586(1982).
31. Harris, E. H. The Chlamydomonas Sourcebook 502 (Academic, New York, 1989).
32. Walther, Z., Vashishlha, M. & Hall, J. L. The Chlamydomonas FLA10 gene encodes a novel kinesin-homologous protein. J. Cell Biol. 126, 175-188 (1994).
33. Goodson, H. V., Kang, S. J. & Endow, S. A. Molecular phylogeny of the kinesin family of microtubule motor proteins. J. Cell Sci. 107, 1875-1884 (1994).
34. Scholey. J. M. Kinesin-II, a membrane traffic motor in axons, axonemes, and spindles. J. Cell Biol. 133, 1-4 (1996).
35. Vashishtha, M., Walther, Z. & Hall, J. L. The kinesin-homologous protein encoded by the Chlamydomonas FLA10 gene is associated with basal bodies and centrioles. J. Cell Sci. 109, 541-549 (1996).
36. Deane, J. A. Cole, D. G., Seeley, E. S., Diener, D. R. & Rosenbaum, J. L. Localization of intraflagellar transport protein IFT52 identifies basal body transitional fibers as the docking site for IFT particles. Curr. Biol. Blot. 11, 1586-1590 (2001).
37. King, S. M. et al. Brain cytoplasmic and flagellar outer arm dyneins share a highly conserved Mr 8, 000 light chain. J. Biol. Chem. 271, 19358-19366 (1996).
38. Espindola, F. S. et al The light chain composition of chicken brain myosin-Va: Calmodulin, myosin-ll essential light chains, and 8-kDa dynein light chain/PIN. Cell Motil. Cytoskeleton 47, 269-281 (2000).
39. Gibbons, B. H., Asai, D. J., Tang, W. J., Hays, T. S. & Gibbons, I. R. Phylogeny and expression of axonemal and cytoplasmic dynein genes in sea urchins. Mol. Biol. Cell 5, 57-70(1994).
40. Tanaka, Y., Zhang, Z. & Hirokawa, N. Identification and molecular evolution of new dynein-like protein sequences in rat brain. J. Cell Sci. 108, 1883-1893 (1995).
41. Porter, M. E., Bower, R., Knott, J. A, Byrd, P. & Dentler, W. Cytoplasmic dynein heavy chain 1b is required for flagellar assembly in Chlamydomonas. Mol. Biol. Cell 10, 693-712 (1999).
42. Pazour, G.J., Dickert, B. L, & Witman, G. B. The DHC1B (DHC2) isoform of cytoplasmic dynein is necessary for flagellar maintenance as well as flagellar assembly. Mol. Biol. Cell 10, 369a (1999).
43. Iomini, C., Babaev-Khalmov, V., Sassaroli, M. & Piperno, G. Protein particles in Chlamydomonas flagella undergo a transport cycle consisting of four phases. J. Cell Biol. 153, 13-24 (2001).
44. Piperno, G. et al. Distinct mutants of retrograde intraflagellar transport (IFT) share similar morphological and molecular defects. J. Cell Biol. 143, 1591-1601 (1998).
45. Reese, E. L. & Haimo, L. T. Dynein, dynactin, and kinesin II's interaction with microtubules is regulated during bi-directional organelle transport. J. Cell Biol. 151, 155-166 (2000).
46. Dentler, W. L. & Rosenbaum, J. L. Flagellar elongation and shortening in Chlamydomonas. J. Cell Biol. 74, 747-759(1977).
47. Dentler, W. L. Structures linking the tips of ciliary and flagellar microtubules to the membrane. J. Cell Sci. 42, 207-220 (1980).
48. Piperno, G. & Mead, K. Transport of a novel complex in the cytoplasmic matrix of Chlamydomonas flagella. Proc. NatlAcad. Sci. USA 94, 4457-4462 (1997).
49. San Agustin, J. T., Pazour, G. J. & Witman, G. B. Intraflagellar transport is essential for mammalian sperm tail formation. Mol. Biol. Cell 12, 446a (2001).
50. Moyer, J. H. et al Candidate gene associated with a mutation causing recessive polycystic kidney disease in mice. Science 264, 1329-1333 (1994).
51. Pazour, G. J., San Agustin, J. T., Follit, J. A., Rosenbaum, J. L. & Witman, G.B. Polycystin-2 is localized to kidney cilia and its ciliary level is elevated in orpk mice with polycystic kidney disease. Curr. Biol. 12, R378-R380 (2002).
52. Miller, M. S. & Cole, D. G. Chlamydomonas IFT172 is homologous to the rat selective LIM domain-binding (SLB) protein, a transcription factor-binding protein. Mol. Biol. Cell 12, 446a (2001).
53. Howard, P. W. & Maurer, R. A. Identification of a conserved protein that interacts with specific LIM homeodomain transcription factors. J. Biol. Chem. 275, 13336-13342(2000).
54. Brazelton, W. J., Amundsen, C. D., Silflow. C. D. & Lefebvre, P A. The bld1 mutation identifies the Chlamydomonas osm-6 homolog as a gene required for flagellar assembly. Curr. Biol. 11, 1591-1594 (2001).
55. Wick, M. J., Ann, D. K. & Loh, H. H. Molecular cloning of a novel protein regulated by opioid treatment of NG108-15 cells. Brain Res. MoL Brain Res. 32, 171-175 (1995).
56. Gervais, F. G. et al. Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi. Nature Cell Biol. 4, 95-105 (2002).
57. Pazour, G. J., Dickert, B. L., Rosenbaum, J. L., Witman, G. B. & Cole, D. G. The p57 subunit of the intraflagellar transport (IFT) complex B is required for flagellar assembly in Chlamydomonas reinhardti. Mol. Biol. Cell 10, 388a(1999).
58. Ringo, D. L. Flagellar motion and fine structure of the flagellar apparatus in Chlamydomonas. J. Cell Biol. 33, 543-571 (1967).
59. Weiss, R. L., Goodenough, D. A. & Goodenough, U. W. Membrane particle arrays associated with the basal body and with contractile vacuole secretion in Chlamydomonas. J. Cell Biol. 72, 133-143 (1977).
60. Bouck, G. B., Rosiere, T. K. & Levasseur, P.J. in Ciliary and Flagellar Membranes (ed. Bloodgood, R. A.), 65-90 (Plenum, New York, 1990).
61. Handel, M. et al. Selective targeting of somatostatin receptor 3 to neuronal cilia. Neuroscience 89, 909-926 (1999).
62. Bloodgood, R. A. Protein targeting to flagella of trypanosomatid protozoa. Cell Biol. Int. 24, 857-862 (2000).
63. Snapp, E. L. & Landfear, S. M. Cytoskeletal association is important for differential targeting of glucose transporter isoforms in Leishmania. J. Cell Biol. 139, 1775-1783 (1997).
64. Snapp, E. L. & Landfear, S. M. Characlerization of a targeting motif for a flagellar membrane protein in Leishmania ennettii. J. Biol. Chem. 274, 29543-29548(1999).
65. Godsel, L. M. & Engman, D. M. Flagellar protein localization mediated by a calcium-myrstoyl/palmitoyl switch mechanism. EMBO J. 18, 2057-2065 (1999).
66. Bouck, G. B. The structure, origin, isolation, and composition of the tubular mastigonemes of the Ochromonas flagellum. J. Cell Biol. 50, 362-384 (1971).
67. Deretic, D. & Papermaster, D. S. Polarized sorting of rhodopsin on post-Golgi membranes in frog retinal photoreceptor cells, J. Cell Biol. 113, 1281-1293 (1991).
68. Fowkes, M. E. & Mitchell, D. R. The role of preassembled cytoplasmic complexes in assembly of flagellar dynein subunits. Mol. Biol. Cell 9, 2337-2347 (1998).
69. Diener, D. R., Cole, D. G. & Rosenbaum, J. L. Cytoplasmic precursors of flagellar radial spokes exist as large complexes. Mol. Biol. Cell7, 47a (1996).
70. Grantham, J. J., Nair, V. & Winklhofer, IF Cystic diseases of the kidney. in Brenner & Rector's The Kidney (ed. Brenner, B. M.), 1699-1730 (W. B. Saunders, Philadelphia, 1996).
71. Blyth, H. & Ockenden, B. G. Polycyslic disease of kidneys and liver presenting in childhood. J. Med. Genet. 8, 257-284 (1971).
72. Cole, B. R., Conley, S. B. & Stapleton, F. B. Polcystic kidney disease in the first year of life. J. Pediatr. 111, 693-699(1987).
73. Taulman, P.D., Haycraft, C. J., Balkovetz, D. F. & Yoder, B. K. Polaris, a protein involved in left-right axis patterning, localizes to basal bodies and cilia. Mol. Biol. Cell 12, 589-599 (2001).
74. Emmons. S. W. & Somlo, S. Mating, channels and kidney cysts. Nature 401, 339-340 (1999).
75. Murcia, N. S., Sweeney, W. E. & Avner, E. D. New insights into the molecular pathophysiology of polycystic kidney disease. Kidney Int. 55, 1187-1197 (1999).
76. Somlo, S. & Ehrlich, B. Calcium signaling in polycystic kidney disease. Curr. Biol. 11, R356-R360 (2001).
77. Barr, M. M. & Sternberg, P. W. A polycystic kidney-disease gene homologue required for male mating behaviour in C. Elegans. Nature 401, 386-389 (1999). A seminal paper that showed that the C. Elegans homologues of polycystin 1 and polycystin 2 are located on the sensory cilia of the nematode.
78. Yoder, B. K., Hou, X. & Guay-Woodford, L. M. The polycystic kidney disease proteins: Polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J. Am. Soc. Nephrol. 13, 2508-2516 (2002).
79. Alberts, B. etal. Molecular Biology of the Cell 3rd Edn. (Garland, New York, 1994).
80. Praetonus, H. A. & Spring, K. R. Bending the MDCK cell primary cilium increases intracellular calcium. J. Membr Biol. 184, 71-79 (2001).
81. Schwartz, E. A., Leonard, M. L., Bizios, R. & Bowser, S. S. Analysis and modeling of the primary cilium bending response to fluid shear. Am. J. Physiol. 272, F132-F138 (1997).
82. De Robertis, E. Morphogenesis of retinal rods: An electron microscope study. J. Biophys. Biochem. Cytol. 2 (suppl.), 209-216 (1958).
83. Tokuyasu, K. & Yamada, E. The fine structure of the retina studied with the electron microscope. IV. Morphogenesis of outer segments of retinal rods. J. Biophys. Biochem. Cytol. 6, 225-230 (1959).
84. Young, R. W. Visual cells and the concept of renewal. Invest. Ophthalmol. Vis. Sci. 15, 700-725 (1976).
85. Besharse, J. C. in The Retina: A Model for Cell Biological Studies Part 1 (eds Adler, R. & Farber, D.) 297-352 (Academic, New York, 1986).
86. Beech, P. L. et al. Localization of kinesin superfamily proteins to the connecting cilium of fish photoreceptors. J. Cell Sci. 109, 889-897 (1996).
87. Traboulsi, E. I. Genetic Diseases of the Eye (Oxford Univ. Press, Oxford, 1998).
88. Sung, C-H. & Tai, A. W. Rhodopsin trafficking and its role in retinal dystrophies. Int. Rev. Cytol. 195, 215-267 (2000).
89. Stephens, R. E. Synthesis and turnover of embryonic sea urchin ciliary proteins during selective inhibition of tubulin synthesis and assembly. Mol. Biol. Cell 11, 2187-2198 (1997).
90. Song, L. & Dentler, W. L. Flagellar protein dynamics in Chlamydomonas. J. Biol. Chem. 10, 29754-29763 (2001).
91. Marshall, W. F. & Rosenbaum, J. L. Intraflagellar transport balances continuous turnover of outer doublet microtubules: Implications for flagellar length control. J. Cell Biol. 155, 405-414 (2001).
92. Bergman, K., Goodenough, U. W., Goodenough, D. A., Jawitz, J. & Martin, H. Gametic differentiation in Chlamydomonas reinhardtii. II. Flagellar membranes and the agglutination reaction. J. Cell Biol. 3, 606-622 (1975).
93. Remillard, S. R & Witman, G. B. Synthesis, transport, and utilization of specific flageller proteins during flagellar regeneration in Chlamydomonas. J. Cell Biol. 93, 615-631 (1982).
94. Bloodgood, R. A. Preferential turnover of membrane proteins in the intact Chlamydomonas flagellum. Exp. Cell Res. 150, 488-493 (1984).
95. Pan, J. & Snell, W. J. Signal transduction during fertilization in the unicellular green alga, Chlamydomonas. Curr. Opin. Microbiol. 6, 596-602 (2000).
96. Pan, J. & Snell, W. J. Kinesin-II is required for flagellar sensory transduction during fertilization in Chlamydomonas. Mol. BioL Cell 13, 1417-1426 (2002).
97. Pan, J. & Snell, W. Regulated targeting of a protein kinase into an intact flagellum. An Aurora/lpl1p-like protein kinase translocates from the cell body into the flagella during gamete activation in Chlamydomonas. J. Biol. Chem. 31, 24106-24114(2000).
98. Pan, J. & Snell, W. J. FLA10 kinesin II and regulated translocation into intact flagella of a protein kinase in Chlamydomonas gametes. Mol. Biol. Cell 11, 868a(2000).
99. Witman, G. B. Introduction to cilia and flagella, in Ciliary and Flagellar Membranes (ed. Bloodgood, R. A.) 1-30 (Plenum, New York, 1990).
100. Whealley, D. N. Primary cilia in normal and pathological tissues. Pathobiology 63, 222-238 (1995).
101. Afzelius, B. A. & Mossberg, B. in The Metabolic and Molecular Bases of Inherited Disease Vol. III (eds Scdver, C. R. et al.) 3943-3954 (McGraw-Hill, New York, 1995).
102. Okada, Y. etal. Abnormal nodal flow precedes situs inversus in iv and inv mice. Mol. Cell 4, 459-468 (1999).
103. Supp, D. M. et al. Targeted deletion of the ATP binding domain of left-right dynein confirms its role in specifying development of left-right asymmetries. Development 126, 5495-5504(1999).
104. Nonaka, S., Shiratori, H., Saijoh, Y. & Hamada, H. Determination of left-right patterning of the mouse embryo by artificial nodal flow. Nature 418, 96-99 (2002).