Primary cilia: Highly sophisticated biological sensors

Sensors

Volumn 9, Issue 9, 2009, Pages 7003-7020

  Alaiwi, Wissam A Abou ^a   Lo, Shao T ^a   Nauli, Surya M ^a  

^a MEDICAL COLLEGE OF OHIO   (United States)

Author keywords

Calcium; Fluid shear stress; Mechanosensory transduction; Primary cilia

Indexed keywords

BIOLOGICAL SENSORS; CELL CYCLE REGULATION; FLUID SHEAR STRESS; MAMMALIAN CELLS; MECHANOSENSORY TRANSDUCTION; PRIMARY CILIA; RENAL EPITHELIA; VASCULAR ENDOTHELIUM;

CALCIUM;

CELL MEMBRANES;

EID: 70350023377     PISSN: 14248220     EISSN: None     Source Type: Journal    
DOI: 10.3390/s90907003     Document Type: Review

References (102)

1. Satir, P.; Christensen, S.T. Structure and function of mammalian cilia. Histochem. Cell. Biol. 2008, 129, 687-693.
2. Wheatley, D.N.; Wang, A.M.; Strugnell, G.E. Expression of primary cilia in mammalian cells. Cell Biol. Int. 1996, 20, 73-81.
3. Nauli, S.M.; Zhou, J. Polycystins and mechanosensation in renal and nodal cilia. Bioessays 2004, 26, 844-856.
4. Rosenbaum, J.L.; Witman, G.B. Intraflagellar transport. Nat. Rev. Mol. Cell Biol. 2002, 3, 813-825.
5. Satir, P.; Christensen, S.T. Overview of structure and function of mammalian cilia. Annu. Rev. Physiol. 2007, 69, 377-400.
6. Gerdes, J.M.; Davis, E.E.; Katsanis, N. The vertebrate primary cilium in development, homeostasis, and disease. Cell 2009, 137, 32-45.
7. Sharma, N.; Berbari, N.F.; Yoder, B.K. Ciliary dysfunction in developmental abnormalities and diseases. Curr. Top Dev. Biol. 2008, 85, 371-427.
8. Sorokin, S. Centrioles and the formation of rudimentary cilia by fibroblasts and smooth muscle cells. J. Cell Biol. 1962, 15, 363-377.
9. Fliegauf, M.; Benzing, T.; Omran, H. When cilia go bad: cilia defects and ciliopathies. Nat. Rev. Mol. Cell Biol. 2007, 8, 880-893.
10. Salathe, M. Regulation of mammalian ciliary beating. Annu. Rev. Physiol. 2007, 69, 401-422.
11. Wanner, A.; Salathe, M.; O'Riordan, T. G. Mucociliary clearance in the airways. Am. J. Respir. Crit. Care Med. 1996, 154, 1868-1902.
12. 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 1993, 90, 5519-5523.
13. Corbit, K.C.; Aanstad, P.; Singla, V.; Norman, A.R.; Stainier, D.Y.; Reiter, J.F. Vertebrate Smoothened functions at the primary cilium. Nature 2005, 437, 1018-1021.
14. Dutcher, S.K. Flagellar assembly in two hundred and fifty easy-to-follow steps. Trends Genet. 1995, 11, 398-404.
15. Gherman, A.; Davis, E.E.; Katsanis, N. The ciliary proteome database: an integrated community resource for the genetic and functional dissection of cilia. Nat. Genet. 2006, 38, 961-962.
16. Liu, Q.; Tan, G.; Levenkova, N.; Li, T.; Pugh, E.N., Jr.; Rux, J.J.; Speicher, D.W.; Pierce, E.A. The proteome of the mouse photoreceptor sensory cilium complex. Mol. Cell Proteomics 2007, 6, 1299-1317.
17. Pazour, G.J.; Agrin, N.; Leszyk, J.; Witman, G.B. Proteomic analysis of a eukaryotic cilium. J. Cell Biol. 2005, 170, 103-113.
18. 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. 1997, 272, F132-F138.
19. Praetorius, H.A.; Spring, K.R. Bending the MDCK cell primary cilium increases intracellular calcium. J. Membr. Biol. 2001, 184, 71-79.
20. Nauli, S.M.; Alenghat, F.J.; Luo, Y.; Williams, E.; Vassilev, P.; Li, X.; Elia, A.E.; Lu, W.; Brown, E.M.; Quinn, S.J.; Ingber, D.E.; Zhou, J. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 2003, 33, 129-137.
21. 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. 2002, 13, 2508-2516.
22. Nauli, S.M.; Rossetti, S.; Kolb, R.J.; Alenghat, F.J.; Consugar, M.B.; Harris, P.C.; Ingber, D.E.; Loghman-Adham, M.; Zhou, J. Loss of polycystin-1 in human cyst-lining epithelia leads to ciliary dysfunction. J. Am. Soc. Nephrol. 2006, 17, 1015-1025.
23. 2+ signaling. Am. J. Physiol. Renal. Physiol. 2007, 292, F930-F945.
24. Xu, C.; Shmukler, B.E.; Nishimura, K.; Kaczmarek, E.; Rossetti, S.; Harris, P.C.; Wandinger- Ness, A.; Bacallao, R.L.; Alper, S.L. Attenuated, flow-induced ATP release contributes to absence of flow-sensitive, purinergic Cai2+ signaling in human ADPKD cyst epithelial cells. Am. J. Physiol. Renal. Physiol. 2009, 296, F1464-F1476.
25. Hou, B.; Kolpakova-Hart, E.; Fukai, N.; Wu, K.; Olsen, B.R. The polycystic kidney disease 1 (Pkd1) gene is required for the responses of osteochondroprogenitor cells to midpalatal suture expansion in mice. Bone 2009, 44, 1121-1133.
26. Xiao, Z.; Zhang, S.; Mahlios, J.; Zhou, G.; Magenheimer, B.S.; Guo, D.; Dallas, S.L.; Maser, R.; Calvet, J.P.; Bonewald, L.; Quarles, L.D. Cilia-like structures and polycystin-1 in osteoblasts/osteocytes and associated abnormalities in skeletogenesis and Runx2 expression. J. Biol. Chem. 2006, 281, 30884-30895.
27. 2+ and cAMP signaling. Gastroenterology 2006, 131, 911-920.
28. McGrath, J.; Somlo, S.; Makova, S.; Tian, X.; Brueckner, M. Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell 2003, 114, 61-73.
29. Nauli, S.M.; Kawanabe, Y.; Kaminski, J.J.; Pearce, W.J.; Ingber, D.E.; Zhou, J. Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1. Circulation 2008, 117, 1161-1171.
30. AbouAlaiwi, W.A.; Takahashi, M.; Mell, B.R.; Jones, T.J.; Ratnam, S.; Kolb, R.J.; Nauli, S.M. Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades. Circ. Res. 2009, 104, 860-869.
31. Boekhoff, I.; Tareilus, E.; Strotmann, J.; Breer, H. Rapid activation of alternative second messenger pathways in olfactory cilia from rats by different odorants. Embo J. 1990, 9, 2453-2458.
32. Nakamura, T.; Gold, G.H. A cyclic nucleotide-gated conductance in olfactory receptor cilia. Nature 1987, 325, 442-444.
33. Elias, R.V.; Sezate, S.S.; Cao, W.; McGinnis, J.F. Temporal kinetics of the light/dark translocation and compartmentation of arrestin and alpha-transducin in mouse photoreceptor cells. Mol. Vis. 2004, 10, 672-681.
34. Li, T.; Snyder, W.K.; Olsson, J.E.; Dryja, T.P. Transgenic mice carrying the dominant rhodopsin mutation P347S: evidence for defective vectorial transport of rhodopsin to the outer segments. Proc. Natl. Acad. Sci. USA 1996, 93, 14176-14181.
35. Zaghloul, N.A.; Katsanis, N. Mechanistic insights into Bardet-Biedl syndrome, a model ciliopathy. J. Clin. Invest. 2009, 119, 428-437.
36. Kolb, R.J.; Nauli, S.M. Ciliary dysfunction in polycystic kidney disease: an emerging model with polarizing potential. Front. Biosci. 2008, 13, 4451-4466.
37. Snell, W.J.; Pan, J.; Wang, Q. Cilia and flagella revealed: from flagellar assembly in Chlamydomonas to human obesity disorders. Cell 2004, 117, 693-697.
38. Tobin, J.L.; Beales, P.L. Bardet-Biedl syndrome: beyond the cilium. Pediatr. Nephrol. 2007, 22, 926-936.
39. Gong, Z.; Son, W.; Chung, Y.D.; Kim, J.; Shin, D.W.; McClung, C.A.; Lee, Y.; Lee, H.W.; Chang, D.J.; Kaang, B.K.; Cho, H.; Oh, U.; Hirsh, J.; Kernan, M.J.; Kim, C. Two interdependent TRPV channel subunits, inactive and Nanchung, mediate hearing in Drosophila. J. Neurosci. 2004, 24, 9059-9066.
40. Tobin, D.; Madsen, D.; Kahn-Kirby, A.; Peckol, E.; Moulder, G.; Barstead, R.; Maricq, A.; Bargmann, C. Combinatorial expression of TRPV channel proteins defines their sensory functions and subcellular localization in C. elegans neurons. Neuron 2002, 35, 307-318.
41. Alenghat, F.J.; Nauli, S.M.; Kolb, R.; Zhou, J.; Ingber, D.E. Global cytoskeletal control of mechanotransduction in kidney epithelial cells. Exp. Cell Res. 2004, 301, 23-30.
42. Anderson, C.T.; Castillo, A.B.; Brugmann, S.A.; Helms, J.A.; Jacobs, C.R.; Stearns, T. Primary cilia: cellular sensors for the skeleton. Anat. Rec. (Hoboken) 2008, 291, 1074-1078.
43. Haycraft, C.J.; Serra, R. Cilia involvement in patterning and maintenance of the skeleton. Curr. Top Dev. Biol. 2008, 85, 303-332.
44. Whitfield, J.F. The solitary (primary) cilium--a mechanosensory toggle switch in bone and cartilage cells. Cell Signal 2008, 20, 1019-1024.
45. Rohatgi, R.; Milenkovic, L.; Scott, M.P. Patched1 regulates hedgehog signaling at the primary cilium. Science 2007, 317, 372-376.
46. Haycraft, C.J.; Banizs, B.; Aydin-Son, Y.; Zhang, Q.; Michaud, E.J.; Yoder, B.K. Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS Genet. 2005, 1, e53.
47. Huangfu, D.; Liu, A.; Rakeman, A.S.; Murcia, N.S.; Niswander, L.; Anderson, K.V. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 2003, 426, 83-87.
48. Moorman, S.J.; Shorr, A.Z. The primary cilium as a gravitational force transducer and a regulator of transcriptional noise. Dev. Dyn. 2008, 237, 1955-1959.
49. Badano, J.L.; Teslovich, T.M.; Katsanis, N. The centrosome in human genetic disease. Nat. Rev. Genet. 2005, 6, 194-205.
50. Pan, J.; Wang, Q.; Snell, W.J. Cilium-generated signaling and cilia-related disorders. Lab. Invest. 2005, 85, 452-463.
51. Hovater, M.B.; Olteanu, D.; Hanson, E.L.; Cheng, N.L.; Siroky, B.; Fintha, A.; Komlosi, P.; Liu, W.; Satlin, L.M.; Bell, P.D.; Yoder, B.K.; Schwiebert, E.M. Loss of apical monocilia on collecting duct principal cells impairs ATP secretion across the apical cell surface and ATPdependent and flow-induced calcium signals. Purinerg. Signal 2008, 4, 155-170.
52. Siroky, B.J.; Ferguson, W.B.; Fuson, A.L.; Xie, Y.; Fintha, A.; Komlosi, P.; Yoder, B.K.; Schwiebert, E.M.; Guay-Woodford, L.M.; Bell, P.D. Loss of primary cilia results in deregulated and unabated apical calcium entry in ARPKD collecting duct cells. Am. J. Physiol. Renal. Physiol. 2006, 290, F1320-F1328.
53. 2+ in human autosomal recessive polycystic kidney disease cyst-lining renal epithelial cells. Am. J. Physiol. Renal. Physiol. 2008, 294, F890-F899.
54. Wang, S.; Zhang, J.; Nauli, S.M.; Li, X.; Starremans, P.G.; Luo, Y.; Roberts, K.A.; Zhou, J. Fibrocystin/polyductin, found in the same protein complex with polycystin-2, regulates calcium responses in kidney epithelia. Mol. Cell Biol. 2007, 27, 3241-3252.
55. Bhunia, A.K.; Piontek, K.; Boletta, A.; Liu, L.; Qian, F.; Xu, P.N.; Germino, F.J.; Germino, G.G. PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell 2002, 109, 157-168.
56. Yamaguchi, T.; Wallace, D.P.; Magenheimer, B.S.; Hempson, S.J.; Grantham, J.J.; Calvet, J.P. Calcium restriction allows cAMP activation of the B-Raf/ERK pathway, switching cells to a cAMP-dependent growth-stimulated phenotype. J. Biol. Chem. 2004, 279, 40419-40430.
57. Aguiari, G.; Trimi, V.; Bogo, M.; Mangolini, A.; Szabadkai, G.; Pinton, P.; Witzgall, R.; Harris, P.C.; Borea, P.A.; Rizzuto, R.; del Senno, L. Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells. Cell Prolif. 2008, 41, 554-573.
58. Battini, L.; Macip, S.; Fedorova, E.; Dikman, S.; Somlo, S.; Montagna, C.; Gusella, G.L. Loss of polycystin-1 causes centrosome amplification and genomic instability. Hum. Mol. Genet. 2008, 17, 2819-2833.
59. Burtey, S.; Riera, M.; Ribe, E.; Pennenkamp, P.; Rance, R.; Luciani, J.; Dworniczak, B.; Mattei, M.G.; Fontes, M. Centrosome overduplication and mitotic instability in PKD2 transgenic lines. Cell Biol. Int. 2008, 32, 1193-1198.
60. Mahjoub, M.R.; Montpetit, B.; Zhao, L.; Finst, R.J.; Goh, B.; Kim, A.C.; Quarmby, L.M. The FA2 gene of Chlamydomonas encodes a NIMA family kinase with roles in cell cycle progression and microtubule severing during deflagellation. J. Cell Sci. 2002, 115, 1759-1768.
61. Bradley, B.A.; Quarmby, L.M. A NIMA-related kinase, Cnk2p, regulates both flagellar length and cell size in Chlamydomonas. J. Cell Sci. 2005, 118, 3317-3326.
62. White, M.C.; Quarmby, L.M. The NIMA-family kinase, Nek1 affects the stability of centrosomes and ciliogenesis. BMC Cell Biol. 2008, doi: 10.1186/1471-2121-9-29.
63. Qin, H.; Wang, Z.; Diener, D.; Rosenbaum, J. Intraflagellar transport protein 27 is a small G protein involved in cell-cycle control. Curr. Biol. 2007, 17, 193-202.
64. Robert, A.; Margall-Ducos, G.; Guidotti, J.E.; Bregerie, O.; Celati, C.; Brechot, C.; Desdouets, C. The intraflagellar transport component IFT88/polaris is a centrosomal protein regulating G1-S transition in non-ciliated cells. J. Cell Sci. 2007, 120, 628-637.
65. McMahon, A.P.; Ingham, P.W.; Tabin, C.J. Developmental roles and clinical significance of hedgehog signaling. Curr. Top Dev. Biol. 2003, 53, 1-114.
66. May, S.R.; Ashique, A.M.; Karlen, M.; Wang, B.; Shen, Y.; Zarbalis, K.; Reiter, J.; Ericson, J.; Peterson, A.S. Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli. Dev. Biol. 2005, 287, 378-389.
67. Rana, A.A.; Barbera, J.P.; Rodriguez, T.A.; Lynch, D.; Hirst, E.; Smith, J.C.; Beddington, R.S. Targeted deletion of the novel cytoplasmic dynein mD2LIC disrupts the embryonic organiser, formation of the body axes and specification of ventral cell fates. Development 2004, 131, 4999-5007.
68. Zhang, Q.; Murcia, N.S.; Chittenden, L.R.; Richards, W.G.; Michaud, E.J.; Woychik, R.P.; Yoder, B.K. Loss of the Tg737 protein results in skeletal patterning defects. Dev. Dyn. 2003, 227, 78-90.
69. Das, G.; Jenny, A.; Klein, T.J.; Eaton, S.; Mlodzik, M. Diego interacts with Prickle and Strabismus/Van Gogh to localize planar cell polarity complexes. Development 2004, 131, 4467-4476.
70. Theisen, H.; Purcell, J.; Bennett, M.; Kansagara, D.; Syed, A.; Marsh, J.L. dishevelled is required during wingless signaling to establish both cell polarity and cell identity. Development 1994, 120, 347-360.
71. Tree, D.R.; Shulman, J.M.; Rousset, R.; Scott, M.P.; Gubb, D.; Axelrod, J.D. Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling. Cell 2002, 109, 371-381.
72. Vinson, C.R.; Adler, P.N. Directional non-cell autonomy and the transmission of polarity information by the frizzled gene of Drosophila. Nature 1987, 329, 549-551.
73. Fischer, E.; Legue, E.; Doyen, A.; Nato, F.; Nicolas, J.F.; Torres, V.; Yaniv, M.; Pontoglio, M. Defective planar cell polarity in polycystic kidney disease. Nat. Genet. 2006, 38, 21-23.
74. Jonassen, J.A.; San Agustin, J.; Follit, J.A.; Pazour, G.J. Deletion of IFT20 in the mouse kidney causes misorientation of the mitotic spindle and cystic kidney disease. J. Cell Biol. 2008, 183, 377-384.
75. Patel, V.; Li, L.; Cobo-Stark, P.; Shao, X.; Somlo, S.; Lin, F.; Igarashi, P. Acute kidney injury and aberrant planar cell polarity induce cyst formation in mice lacking renal cilia. Hum. Mol. Genet. 2008, 17, 1578-1590.
76. Saburi, S.; Hester, I.; Fischer, E.; Pontoglio, M.; Eremina, V.; Gessler, M.; Quaggin, S.E.; Harrison, R.; Mount, R.; McNeill, H. Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease. Nat. Genet. 2008, 40, 1010-1015.
77. Simons, M.; Gloy, J.; Ganner, A.; Bullerkotte, A.; Bashkurov, M.; Kronig, C.; Schermer, B.; Benzing, T.; Cabello, O.A.; Jenny, A.; Mlodzik, M.; Polok, B.; Driever, W.; Obara, T.; Walz, G. Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat. Genet. 2005, 37, 537-543.
78. Yoder, B.K. Role of primary cilia in the pathogenesis of polycystic kidney disease. J. Am. Soc. Nephrol. 2007, 18, 1381-1388.
79. Moyer, J.H.; Lee-Tischler, M.J.; Kwon, H.Y.; Schrick, J.J.; Avner, E.D.; Sweeney, W.E.; Godfrey, V.L.; Cacheiro, N.L.; Wilkinson, J.E.; Woychik, R.P. Candidate gene associated with a mutation causing recessive polycystic kidney disease in mice. Science 1994, 264, 1329-1333.
80. Hateboer, N.; Veldhuisen, B.; Peters, D.; Breuning, M.H.; San-Millan, J.L.; Bogdanova, N.; Coto, E.; van Dijk, M.A.; Afzal, A.R.; Jeffery, S.; Saggar-Malik, A.K.; Torra, R.; Dimitrakov, D.; Martinez, I.; de Castro, S.S.; Krawczak, M.; Ravine, D. Location of mutations within the PKD2 gene influences clinical outcome. Kidney Int. 2000, 57, 1444-1451.
81. Hierck, B.P.; van der Heiden, K.; Alkemade, F.E.; van de Pas, S.; van Thienen, J.V.; Groenendijk, B.C.; Bax, W.H.; van der Laarse, A.; Deruiter, M.C.; Horrevoets, A.J.; Poelmann, R.E. Primary cilia sensitize endothelial cells for fluid shear stress. Dev. Dyn. 2008, 237, 725-735.
82. Poelmann, R.E.; van der Heiden, K.; Gittenberger-de Groot, A.C.; Hierck, B.P. Deciphering the endothelial shear stress sensor. Circulation 2008, 117, 1124-1126.
83. van der Heiden, K.; Groenendijk, B.C.; Hierck, B.P.; Hogers, B.; Koerten, H.K.; Mommaas, A.M.; Gittenberger-de Groot, A.C.; Poelmann, R.E. Monocilia on chicken embryonic endocardium in low shear stress areas. Dev. Dyn. 2006, 235, 19-28.
84. Van der Heiden, K.; Hierck, B.P.; Krams, R.; de Crom, R.; Cheng, C.; Baiker, M.; Pourquie, M.J.; Alkemade, F.E.; DeRuiter, M.C.; Gittenberger-de Groot, A.C.; Poelmann, R. E. Endothelial primary cilia in areas of disturbed flow are at the base of atherosclerosis. Atherosclerosis 2008, 196, 542-550.
85. Schneider, L.; Clement, C.A.; Teilmann, S.C.; Pazour, G.J.; Hoffmann, E.K.; Satir, P.; Christensen, S.T. PDGFRalphaalpha signaling is regulated through the primary cilium in fibroblasts. Curr. Biol. 2005, 15, 1861-1866.
86. Alvarez, R.H.; Kantarjian, H.M.; Cortes, J.E. Biology of platelet-derived growth factor and its involvement in disease. Mayo Clin. Proc. 2006, 81, 1241-1257.
87. Yu, J.; Ustach, C.; Kim, H.R. Platelet-derived growth factor signaling and human cancer. J. Biochem. Mol. Biol. 2003, 36, 49-59.
88. Mao, J.H.; Wu, D.; Perez-Losada, J.; Jiang, T.; Li, Q.; Neve, R.M.; Gray, J.W.; Cai, W.W.; Balmain, A. Crosstalk between Aurora-A and p53: frequent deletion or downregulation of Aurora-A in tumors from p53 null mice. Cancer Cell 2007, 11, 161-173.
89. Portier, N.; Audhya, A.; Maddox, P.S.; Green, R.A.; Dammermann, A.; Desai, A.; Oegema, K. A microtubule-independent role for centrosomes and aurora a in nuclear envelope breakdown. Dev. Cell 2007, 12, 515-529.
90. Pugacheva, E.N.; Golemis, E.A. The focal adhesion scaffolding protein HEF1 regulates activation of the Aurora-A and Nek2 kinases at the centrosome. Nat. Cell Biol. 2005, 7, 937-946.
91. Pugacheva, E.N.; Jablonski, S.A.; Hartman, T.R.; Henske, E.P.; Golemis, E.A. HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 2007, 129, 1351-1363.
92. Thoma, C.R.; Frew, I.J.; Hoerner, C.R.; Montani, M.; Moch, H.; Krek, W. pVHL and GSK3beta are components of a primary cilium-maintenance signalling network. Nat. Cell Biol. 2007, 9, 588-595.
93. Badano, J.L.; Mitsuma, N.; Beales, P.L.; Katsanis, N. The ciliopathies: an emerging class of human genetic disorders. Annu. Rev. Genom. Hum. Genet. 2006, 7, 125-148.
94. Hildebrandt, F.; Otto, E. Cilia and centrosomes: A unifying pathogenic concept for cystic kidney disease? Nat. Rev. Genet. 2005, 6, 928-940.
95. Praetorius, H.A.; Spring, K.R. A physiological view of the primary cilium. Annu. Rev. Physiol. 2005, 67, 515-529.
96. Masyuk, A.I.; Masyuk, T.V.; LaRusso, N.F. Cholangiocyte primary cilia in liver health and disease. Dev. Dyn. 2008, 237, 2007-2012.
97. Hong, D.H.; Pawlyk, B.; Sokolov, M.; Strissel, K.J.; Yang, J.; Tulloch, B.; Wright, A.F.; Arshavsky, V.Y.; Li, T. RPGR isoforms in photoreceptor connecting cilia and the transitional zone of motile cilia. Invest. Ophthal. Mol. Vis. Sci. 2003, 44, 2413-2421.
98. Beales, P.L. Lifting the lid on Pandora's box: the Bardet-Biedl syndrome. Curr. Opin. Genet. Dev. 2005, 15, 315-323.
99. Katsanis, N.; Beales, P.L.; Woods, M.O.; Lewis, R.A.; Green, J.S.; Parfrey, P.S.; Ansley, S.J.; Davidson, W.S.; Lupski, J.R. Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome. Nat. Genet. 2000, 26, 67-70.
100. Maffei, P.; Munno, V.; Marshall, J.D.; Scandellari, C.; Sicolo, N. The Alstrom syndrome: Is it a rare or unknown disease? Ann. Ital. Med. Int. 2002, 17, 221-228.
101. Kulaga, H.M.; Leitch, C.C.; Eichers, E.R.; Badano, J.L.; Lesemann, A.; Hoskins, B.E.; Lupski, J.R.; Beales, P.L.; Reed, R.R.; Katsanis, N. Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse. Nat. Genet. 2004, 36, 994-998.
102. Adato, A.; Lefevre, G.; Delprat, B.; Michel, V.; Michalski, N.; Chardenoux, S.; Weil, D.; El-Amraoui, A.; Petit, C. Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells. Hum. Mol. Genet. 2005, 14, 3921-3932.