Cilia, Wnt signaling, and the cytoskeleton

Cilia

Matthew W Kelley¹  Helen L May-Simera¹ 

[1] Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, NIH, 35 Convent Drive. Bethesda, MD 20892, USA

关键词: GTPases;    kinesins;    cytoskeleton;    actin;    microtubules;    β-catenin;    PCP;    Wnt signaling;    basal body;    Cilia;   

Others  :  793538
DOI  :  10.1186/2046-2530-1-7

 received in 2011-10-11, accepted in 2012-05-02,  发布年份 2012

【 摘 要 】

Primary cilia have recently been highlighted as key regulators in development and disease. This review focuses on current work demonstrating the broad role of cilia-related proteins in developmental signaling systems. Of particular consideration is the importance of the basal body region, located at the base of the cilium, in its role as a focal point for many signaling pathways and as a microtubule organizing center. As the cilium is effectively a microtubular extension of the cytoskeleton, investigating connections between the cilium and the cytoskeleton provides greater insight into signaling and cell function. Of the many signaling pathways associated with primary cilia, the most extensively studied in association with the cytoskeleton and cytoskeletal rearrangements are both canonical and non-canonical Wnt pathways. One of the key concepts currently emerging is a possible additional role for the traditionally 'cilia-related' proteins in other aspects of cellular processes. In many cases, disruption of such processes manifests at the level of the cilium. While the involvement of cilia and cilia-related proteins in signaling pathways is currently being unraveled, there is a growing body of evidence to support the notion that ciliary proteins are required not only for regulation of Wnt signaling, but also as downstream effectors of Wnt signaling. This review summarizes recent advances in our understanding of the involvement of cilia and basal body proteins in Wnt signaling pathways.

【 授权许可】

   
2012 May-Simera and Kelley; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Baker K, Beales PL: Making sense of cilia in disease: the human ciliopathies. Am J Med Genet C Semin Med Genet 2009, 151C:281-295.
• [2]Ware SM, Aygun MG, Hildebrandt F: Spectrum of clinical diseases caused by disorders of primary cilia. Proc Am Thorac Soc 2011, 8:444-450.
• [3]Lee L: Mechanisms of mammalian ciliary motility: Insights from primary ciliary dyskinesia genetics. Gene 2011, 473:57-66.
• [4]Singla V, Reiter JF: The primary cilium as the cell's antenna: signaling at a sensory organelle. Science 2006, 313:629-633.
• [5]Berbari NF, O'Connor AK, Haycraft CJ, Yoder BK: The primary cilium as a complex signaling center. Curr Biol 2009, 19:R526-535.
• [6]Ishikawa H, Marshall WF: Ciliogenesis: building the cell's antenna. Nat Rev Mol Cell Biol 2011, 12:222-234.
• [7]Wallingford JB, Mitchell B: Strange as it may seem: the many links between Wnt signaling, planar cell polarity, and cilia. Genes Dev 2011, 25:201-213.
• [8]Marshall WF: What is the function of centrioles? J Cell Biochem 2007, 100:916-922.
• [9]Nigg EA: Centrosome duplication: of rules and licenses. Trends Cell Biol 2007, 17:215-221.
• [10]Fisch C, Dupuis-Williams P: Ultrastructure of cilia and flagella - back to the future! Biol Cell 2011, 103:249-270.
• [11]Sang L, Miller JJ, Corbit KC, Giles RH, Brauer MJ, Otto EA, Baye LM, Wen X, Scales SJ, Kwong M, Huntzicker EG, Skafianos MK, Sandoval W, Bazan JF, Kulkarni P, Garcia-Gonzalo FR, Seol AD, O'Toole JF, Held S, Reutter HM, Lane WS, Rafiq MA, Noor A, Ansar M, Devi AR, Sheffield VC, Slusarski DC, Vincent JB, Doherty DA, Hildebrandt F, et al.: Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell 2011, 145:513-528.
• [12]Rosenbaum JL, Witman GB: Intraflagellar Transport. Nat Rev Mol Cell Biol 2002, 3:813-825.
• [13]Craige B, Tsao CC, Diener DR, Hou Y, Lechtreck KF, Rosenbaum JL, Witman GB: CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content. J Cell Biol 2010, 190:927-940.
• [14]Nachury MV, Loktev AV, Zhang Q, Westlake CJ, Peranen J, Merdes A, Slusarski DC, Scheller RH, Bazan JF, Sheffield VC, Jackson PK: A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell 2007, 129:1201-1213.
• [15]Scholey JM: Intraflagellar transport motors in cilia: moving along the cell's antenna. J Cell Biol 2008, 180:23-29.
• [16]Seo S, Baye LM, Schulz NP, Beck JS, Zhang Q, Slusarski DC, Sheffield VC: BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. Proc Natl Acad Sci USA 2010, 107:1488-1493.
• [17]Waters AM, Beales PL: Ciliopathies: an expanding disease spectrum. Pediatr Nephrol 2011, 26:1039-1056.
• [18]Williams CL, Li C, Kida K, Inglis PN, Mohan S, Semenec L, Bialas NJ, Stupay RM, Chen N, Blacque OE, Yoder BK, Leroux MR: MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis. J Cell Biol 2011, 192:1023-1041.
• [19]Lancaster MA, Gopal DJ, Kim J, Saleem SN, Silhavy JL, Louie CM, Thacker BE, Williams Y, Zaki MS, Gleeson JG: Defective Wnt-dependent cerebellar midline fusion in a mouse model of Joubert syndrome. Nat Med 2011, 17:726-731.
• [20]Coppieters F, Lefever S, Leroy BP, De Baere E: CEP290, a gene with many faces: mutation overview and presentation of CEP290base. Hum Mutat 2010, 31:1097-1108.
• [21]Zaghloul NA, Katsanis N: Functional modules, mutational load and human genetic disease. Trends Genet 2010, 26:168-176.
• [22]Lidow MS, Menco BP: Observations on axonemes and membranes of olfactory and respiratory cilia in frogs and rats using tannic acid-supplemented fixation and photographic rotation. J Ultrastruct Res 1984, 86:18-30.
• [23]Nonaka S, Tanaka Y, Okada Y, Takeda S, Harada A, Kanai Y, Kido M, Hirokawa N: Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell 1998, 95:829-837.
• [24]McGarth 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.
• [25]Shah AS, Ben-Shahar Y, Moninger TO, Kline JN, Welsh MJ: Motile cilia of human airway epithelia are chemosensory. Science 2009, 325:1131-1134.
• [26]Zizzari ZV, Lupetti P, Mencarelli C, Dallai R: Sperm ultrastructure and spermiogenesis of Coniopterygidae (Neuroptera, Insecta). Arthropod Struct Dev 2008, 37:410-417.
• [27]May-Simera HL, Ross A, Rix S, Forge A, Beales PL, Jagger DJ: Patterns of expression of Bardet-Biedl syndrome proteins in the mammalian cochlea suggest noncentrosomal functions. J Comp Neurol 2009, 514:174-188.
• [28]Finetti F, Paccani SR, Riparbelli MG, Giacomello E, Perinetti G, Pazour GJ, Rosenbaum JL, Baldari CT: Intraflagellar transport is required for polarized recycling of the TCR/CD3 complex to the immune synapse. Nat Cell Biol 2009, 11:1332-1339.
• [29]Delaval B, Bright A, Lawson ND, Doxsey S: The cilia protein IFT88 is required for spindle orientation in mitosis. Nat Cell Biol 2011, 13:461-468.
• [30]Kim S, Tsiokas L: Cilia and cell cycle re-entry: more than a coincidence. Cell Cycle 2011, 10:2683-2690.
• [31]Sorokin S: Centrioles and the formation of rudimentary cilia by fibroblasts and smooth muscle cells. J Cell Biol 1962, 15:363-377.
• [32]Santos N, Reiter JF: Building it up and taking it down: the regulation of vertebrate ciliogenesis. Dev Dyn 2008, 237:1972-1981.
• [33]Pedersen LB, Veland IR, Schroder JM, Christensen ST: Assembly of primary cilia. Dev Dyn 2008, 237:1993-2006.
• [34]Follit JA, Tuft RA, Fogarty KE, Pazour GJ: The intraflagellar transport protein IFT20 is associated with the Golgi complex and is required for cilia assembly. Mol Biol Cell 2006, 17:3781-3792.
• [35]Follit JA, San Agustin JT, Xu F, Jonassen JA, Samtani R, Lo CW, Pazour GJ: The Golgin GMAP210/TRIP11 anchors IFT20 to the Golgi complex. PLoS Genet 2008, 4:e1000315.
• [36]Sedmak T, Wolfrum U: Intraflagellar transport molecules in ciliary and nonciliary cells of the retina. J Cell Biol 2010, 189:171-186.
• [37]Willardsen MI, Link BA: Cell biological regulation of division fate in vertebrate neuroepithelial cells. Dev Dyn 2011, 240:1865-1879.
• [38]Vorobjev IA, Chentsov Yu S: Centrioles in the cell cycle. I. Epithelial cells. J Cell Biol 1982, 93:938-949.
• [39]Anderson CT, Stearns T: Centriole age underlies asynchronous primary cilium growth in mammalian cells. Curr Biol 2009, 19:1498-1502.
• [40]Kobayashi T, Dynlacht BD: Regulating the transition from centriole to basal body. J Cell Biol 2011, 193:435-444.
• [41]Yamashita YM, Fuller MT: Asymmetric stem cell division and function of the niche in the Drosophila male germ line. Int J Hematol 2005, 82:377-380.
• [42]Yamashita YM, Mahowald AP, Perlin JR, Fuller MT: Asymmetric inheritance of mother versus daughter centrosome in stem cell division. Science 2007, 315:518-521.
• [43]Yamashita YM, Fuller MT: Asymmetric centrosome behavior and the mechanisms of stem cell division. J Cell Biol 2008, 180:261-266.
• [44]Spektor A, Tsang WY, Khoo D, Dynlacht BD: Cep97 and CP110 suppress a cilia assembly program. Cell 2007, 130:678-690.
• [45]Tsang WY, Bossard C, Khanna H, Peranen J, Swaroop A, Malhotra V, Dynlacht BD: CP110 suppresses primary cilia formation through its interaction with CEP290, a protein deficient in human ciliary disease. Dev Cell 2008, 15:187-197.
• [46]Kobayashi T, Tsang WY, Li J, Lane W, Dynlacht BD: Centriolar kinesin Kif24 interacts with CP110 to remodel microtubules and regulate ciliogenesis. Cell 2011, 145:914-925.
• [47]Park TJ, Mitchell BJ, Abitua PB, Kintner C, Wallingford JB: Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells. Nat Genet 2008, 40:871-879.
• [48]Kim S, Zaghloul NA, Bubenshchikova E, Oh EC, Rankin S, Katsanis N, Obara T, Tsiokas L: Nde1-mediated inhibition of ciliogenesis affects cell cycle re-entry. Nat Cell Biol 2011, 13:351-360.
• [49]Li A, Saito M, Chuang JZ, Tseng YY, Dedesma C, Tomizawa K, Kaitsuka T, Sung CH: Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors. Nat Cell Biol 2011, 13:402-411.
• [50]Robert A, Margall-Ducos G, Guidotti JE, 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.
• [51]Ocbina PJ, Tuson M, Anderson KV: Primary cilia are not required for normal canonical Wnt signaling in the mouse embryo. PLoS One 2009, 4:e6839.
• [52]Huang P, Schier AF: Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia. Development 2009, 136:3089-3098.
• [53]Huangfu D, Liu A, Rakeman AS, Murcia NS, Niswander L, Anderson KV: Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 2003, 426:83-87.
• [54]Goetz SC, Anderson KV: The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet 2010, 11:331-344.
• [55]Rix S, Calmont A, Scambler PJ, Beales PL: An Ift80 mouse model of short rib polydactyly syndromes shows defects in hedgehog signalling without loss or malformation of cilia. Hum Mol Genet 2011, 20:1306-1314.
• [56]Dafinger C, Liebau MC, Elsayed SM, Hellenbroich Y, Boltshauser E, Korenke GC, Fabretti F, Janecke AR, Ebermann I, Nurnberg G, Nurnberg P, Zentgraf H, Koerber F, Addicks K, Elsobky E, Benzing T, Schermer B, Bolz HJ: Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubule dynamics. J Clin Invest 2011, 121:2662-2667.
• [57]Qin J, Lin Y, Norman RX, Ko HW, Eggenschwiler JT: Intraflagellar transport protein 122 antagonizes Sonic Hedgehog signaling and controls ciliary localization of pathway components. Proc Natl Acad Sci USA 2011, 108:1456-1461.
• [58]Hong SK, Dawid IB: FGF-dependent left-right asymmetry patterning in zebrafish is mediated by Ier2 and Fibp1. Proc Natl Acad Sci USA 2009, 106:2230-2235.
• [59]Tanaka Y, Okada Y, Hirokawa N: FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination. Nature 2005, 435:172-177.
• [60]Ezratty EJ, Stokes N, Chai S, Shah AS, Williams SE, Fuchs E: A role for the primary cilium in notch signaling and epidermal differentiation during skin development. Cell 2011, 145:1129-1141.
• [61]Marcet B, Chevalier B, Luxardi G, Coraux C, Zaragosi LE, Cibois M, Robbe-Sermesant K, Jolly T, Cardinaud B, Moreilhon C, Giovannini-Chami L, Nawrocki-Raby B, Birembaut P, Waldmann R, Kodjabachian L, Barbry P: Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway. Nat Cell Biol 2011, 13:693-699.
• [62]Boehlke C, Kotsis F, Patel V, Braeg S, Voelker H, Bredt S, Beyer T, Janusch H, Hamann C, Godel M, Muller K, Herbst M, Hornung M, Doerken M, Kottgen M, Nitschke R, Igarashi P, Walz G, Kuehn EW: Primary cilia regulate mTORC1 activity and cell size through Lkb1. Nat Cell Biol 2010, 12:1115-1122.
• [63]Schneider L, Clement CA, Teilmann SC, Pazour GJ, Hoffmann EK, Satir P, Christensen ST: PDGFRalphaalpha signaling is regulated through the primary cilium in fibroblasts. Curr Biol 2005, 15:1861-1866.
• [64]Habbig S, Bartram MP, Muller RU, Schwarz R, Andriopoulos N, Chen S, Sagmuller JG, Hoehne M, Burst V, Liebau MC, Reinhardt HC, Benzing T, Schermer B: NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway. J Cell Biol 2011.
• [65]Otto EA, Schermer B, Obara T, O'Toole JF, Hiller KS, Mueller AM, Ruf RG, Hoefele J, Beekmann F, Landau D, Foreman JW, Goodship JA, Strachan T, Kispert A, Wolf MT, Gagnadoux MF, Nivet H, Antignac C, Walz G, Drummond IA, Benzing T, Hildebrandt F: Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination. Nat Genet 2003, 34:413-420.
• [66]Simons M, Gloy J, Ganner A, Bullerkotte A, Bashkurov M, Kronig C, Schermer B, Benzing T, Cabello OA, 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.
• [67]Lienkamp S, Ganner A, Walz G: Inversin, Wnt signaling and primary cilia. Differentiation 2011, 82:S49-55.
• [68]Gerdes JM, Liu Y, Zaghloul NA, Leitch CC, Lawson SS, Kato M, Beachy PA, Beales PL, Demartino GN, Fisher S, Badano JL, Katsanis N: Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response. Nat Genet 2007, 39:1350-1360.
• [69]Corbit KC, Shyer AE, Dowdle WE, Gaulden J, Singla V, Chen MH, Chuang PT, Reiter JF: Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms. Nat Cell Biol 2008, 10:70-76.
• [70]McDermott KM, Liu BY, Tlsty TD, Pazour GJ: Primary cilia regulate branching morphogenesis during mammary gland development. Curr Biol 2010, 20:731-737.
• [71]Takemaru K, Yamaguchi S, Lee YS, Zhang Y, Carthew RW, Moon RT: Chibby, a nuclear beta-catenin-associated antagonist of the Wnt/Wingless pathway. Nature 2003, 422:905-909.
• [72]Li FQ, Mofunanya A, Harris K, Takemaru K: Chibby cooperates with 14-3-3 to regulate beta-catenin subcellular distribution and signaling activity. J Cell Biol 2008, 181:1141-1154.
• [73]Voronina VA, Takemaru K, Treuting P, Love D, Grubb BR, Hajjar AM, Adams A, Li FQ, Moon RT: Inactivation of Chibby affects function of motile airway cilia. J Cell Biol 2009, 185:225-233.
• [74]Kishimoto N, Cao Y, Park A, Sun Z: Cystic kidney gene seahorse regulates cilia-mediated processes and Wnt pathways. Developmental cell 2008, 14:954-961.
• [75]Willemarck N, Rysman E, Brusselmans K, Van Imschoot G, Vanderhoydonc F, Moerloose K, Lerut E, Verhoeven G, van Roy F, Vleminckx K, Swinnen JV: Aberrant activation of fatty acid synthesis suppresses primary cilium formation and distorts tissue development. Cancer Res 2010, 70:9453-9462.
• [76]Vladar EK, Antic D, Axelrod JD: Planar cell polarity signaling: the developing cell's compass. Cold Spring Harb Perspect Biol 2009, 1:a002964.
• [77]McNeill H: Planar cell polarity: keeping hairs straight is not so simple. Cold Spring Harb Perspect Biol 2010, 2:a003376.
• [78]Ybot-Gonzalez P, Savery D, Gerrelli D, Signore M, Mitchell CE, Faux CH, Greene ND, Copp AJ: Convergent extension, planar-cell-polarity signalling and initiation of mouse neural tube closure. Development 2007, 134:789-799.
• [79]Montcouquiol M, Rachel RA, Lanford PJ, Copeland NG, Jenkins NA, Kelley MW: Identification of Vangl2 and Scrb1 as planar polarity genes in mammals. Nature 2003, 423:173-177.
• [80]Devenport D, Fuchs E: Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles. Nat Cell Biol 2008, 10:1257-1268.
• [81]Jones C, Roper VC, Foucher I, Qian D, Banizs B, Petit C, Yoder BK, Chen P: Ciliary proteins link basal body polarization to planar cell polarity regulation. Nat Genet 2008, 40:69-77.
• [82]Ross AJ, May-Simera H, Eichers ER, Kai M, Hill J, Jagger DJ, Leitch CC, Chapple JP, Munro PM, Fisher S, Tan PL, Phillips HM, Leroux MR, Henderson DJ, Murdoch JN, Copp AJ, Eliot MM, Lupski JR, Kemp DT, Dollfus H, Tada M, Katsanis N, Forge A, Beales PL: Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat Genet 2005, 37:1135-1140.
• [83]Mitchell B, Stubbs JL, Huisman F, Taborek P, Yu C, Kintner C: The PCP pathway instructs the planar orientation of ciliated cells in the Xenopus larval skin. Curr Biol 2009, 19:924-929.
• [84]Antic D, Stubbs JL, Suyama K, Kintner C, Scott MP, Axelrod JD: Planar cell polarity enables posterior localization of nodal cilia and left-right axis determination during mouse and Xenopus embryogenesis. PLoS One 2010, 5:e8999.
• [85]Borovina A, Superina S, Voskas D, Ciruna B: Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia. Nat Cell Biol 2010, 12:407-412.
• [86]Song H, Hu J, Chen W, Elliott G, Andre P, Gao B, Yang Y: Planar cell polarity breaks bilateral symmetry by controlling ciliary positioning. Nature 2010, 466:378-382.
• [87]Fischer E, Legue E, Doyen A, Nato F, Nicolas JF, Torres V, Yaniv M, Pontoglio M: Defective planar cell polarity in polycystic kidney disease. Nat Genet 2006, 38:21-23.
• [88]Cui C, Chatterjee B, Francis D, Yu Q, SanAgustin JT, Francis R, Tansey T, Henry C, Wang B, Lemley B, Pazour GJ, Lo CW: Disruption of Mks1 localization to the mother centriole causes cilia defects and developmental malformations in Meckel-Gruber syndrome. Dis Model Mech 2011, 4:43-56.
• [89]Jonassen JA, San Agustin J, Follit JA, Pazour GJ: Deletion of IFT20 in the mouse kidney causes misorientation of the mitotic spindle and cystic kidney disease. J Cell Biol 2008, 183:377-384.
• [90]Tammachote R, Hommerding CJ, Sinders RM, Miller CA, Czarnecki PG, Leightner AC, Salisbury JL, Ward CJ, Torres VE, Gattone VH, Harris PC: Ciliary and centrosomal defects associated with mutation and depletion of the Meckel syndrome genes MKS1 and MKS3. Hum Mol Genet 2009, 18:3311-3323.
• [91]Jonassen JA, Sanagustin J, Baker SP, Pazour GJ: Disruption of IFT Complex A causes cystic kidneys without mitotic spindle misorientation. J Am Soc Nephrol, in press.
• [92]Nishio S, Tian X, Gallagher AR, Yu Z, Patel V, Igarashi P, Somlo S: Loss of oriented cell division does not initiate cyst formation. J Am Soc Nephrol 2010, 21:295-302.
• [93]Saburi S, Hester I, Fischer E, Pontoglio M, Eremina V, Gessler M, Quaggin SE, 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.
• [94]Park CC, Ahn S, Bloom JS, Lin A, Wang RT, Wu T, Sekar A, Khan AH, Farr CJ, Lusis AJ, Leahy RM, Lange K, Smith DJ: Fine mapping of regulatory loci for mammalian gene expression using radiation hybrids. Nat Genet 2008, 40:421-429.
• [95]Borovina A, Superina S, Voskas D, Ciruna B: Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia. Nat Cell Biol 12:407-412.
• [96]Guirao B, Meunier A, Mortaud S, Aguilar A, Corsi JM, Strehl L, Hirota Y, Desoeuvre A, Boutin C, Han YG, Mirzadeh Z, Cremer H, Montcouquiol M, Sawamoto K, Spassky N: Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia. Nat Cell Biol 2010, 12:341-350.
• [97]May-Simera HL, Kai M, Hernandez V, Osborn DP, Tada M, Beales PL: Bbs8, together with the planar cell polarity protein Vangl2, is required to establish left-right asymmetry in zebrafish. Dev Biol 2010, 345:215-225.
• [98]Kotsis F, Nitschke R, Doerken M, Walz G, Kuehn EW: Flow modulates centriole movements in tubular epithelial cells. Pflugers Arch 2008, 456:1025-1035.
• [99]Kim JC, Badano JL, Sibold S, Esmail MA, Hill J, Hoskins BE, Leitch CC, Venner K, Ansley SJ, Ross AJ, Leroux MR, Katsanis N, Beales PL: The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression. Nat Genet 2004, 36:462-470.
• [100]Park TJ, Haigo SL, Wallingford JB: Ciliogenesis defects in embryos lacking inturned or fuzzy function are associated with failure of planar cell polarity and Hedgehog signaling. Nat Genet 2006, 38:303-311.
• [101]Kim SK, Shindo A, Park TJ, Oh EC, Ghosh S, Gray RS, Lewis RA, Johnson CA, Attie-Bittach T, Katsanis N, Wallingford JB: Planar cell polarity acts through septins to control collective cell movement and ciliogenesis. Science 2010, 329:1337-1340.
• [102]Lee K, Battini L, Gusella GL: Cilium, centrosome and cell cycle regulation in polycystic kidney disease. Biochim Biophys Acta 2011, 1812:1263-1271.
• [103]Narimatsu M, Bose R, Pye M, Zhang L, Miller B, Ching P, Sakuma R, Luga V, Roncari L, Attisano L, Wrana JL: Regulation of planar cell polarity by Smurf ubiquitin ligases. Cell 2009, 137:295-307.
• [104]Jakobsen L, Vanselow K, Skogs M, Toyoda Y, Lundberg E, Poser I, Falkenby LG, Bennetzen M, Westendorf J, Nigg EA, Uhlen M, Hyman AA, Andersen JS: Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods. EMBO J 2011, 30:1520-1535.
• [105]van Amerongen R, Nusse R: Towards an integrated view of Wnt signaling in development. Development 2009, 136:3205-3214.
• [106]Lancaster MA, Louie CM, Silhavy JL, Sintasath L, Decambre M, Nigam SK, Willert K, Gleeson JG: Impaired Wnt-beta-catenin signaling disrupts adult renal homeostasis and leads to cystic kidney ciliopathy. Nat Med 2009, 15:1046-1054.
• [107]Akiyama T, Kawasaki Y: Wnt signalling and the actin cytoskeleton. Oncogene 2006, 25:7538-7544.
• [108]Bienz M: The subcellular destinations of APC proteins. Nat Rev Mol Cell Biol 2002, 3:328-338.
• [109]Mimori-Kiyosue Y, Shiina N, Tsukita S: Adenomatous polyposis coli (APC) protein moves along microtubules and concentrates at their growing ends in epithelial cells. J Cell Biol 2000, 148:505-518.
• [110]Nathke IS, Adams CL, Polakis P, Sellin JH, Nelson WJ: The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration. J Cell Biol 1996, 134:165-179.
• [111]Reilein A, Nelson WJ: APC is a component of an organizing template for cortical microtubule networks. Nat Cell Biol 2005, 7:463-473.
• [112]Su LK, Burrell M, Hill DE, Gyuris J, Brent R, Wiltshire R, Trent J, Vogelstein B, Kinzler KW: APC binds to the novel protein EB1. Cancer Res 1995, 55:2972-2977.
• [113]Nakamura M, Zhou XZ, Lu KP: Critical role for the EB1 and APC interaction in the regulation of microtubule polymerization. Curr Biol 2001, 11:1062-1067.
• [114]Jaulin F, Kreitzer G: KIF17 stabilizes microtubules and contributes to epithelial morphogenesis by acting at MT plus ends with EB1 and APC. J Cell Biol 2010, 190:443-460.
• [115]Schroder JM, Larsen J, Komarova Y, Akhmanova A, Thorsteinsson RI, Grigoriev I, Manguso R, Christensen ST, Pedersen SF, Geimer S, Pedersen LB: EB1 and EB3 promote cilia biogenesis by several centrosome-related mechanisms. J Cell Sci 2011, 124:2539-2551.
• [116]Pedersen LB, Geimer S, Sloboda RD, Rosenbaum JL: The Microtubule plus end-tracking protein EB1 is localized to the flagellar tip and basal bodies in Chlamydomonas reinhardtii. Curr Biol 2003, 13:1969-1974.
• [117]Louie RK, Bahmanyar S, Siemers KA, Votin V, Chang P, Stearns T, Nelson WJ, Barth AI: Adenomatous polyposis coli and EB1 localize in close proximity of the mother centriole and EB1 is a functional component of centrosomes. J Cell Sci 2004, 117:1117-1128.
• [118]Bornens M: Centrosome composition and microtubule anchoring mechanisms. Curr Opin Cell Biol 2002, 14:25-34.
• [119]Blacque OE, Cevik S, Kaplan OI: Intraflagellar transport: from molecular characterisation to mechanism. Front Biosci 2008, 13:2633-2652.
• [120]Daire V, Pous C: Kinesins and protein kinases: Key players in the regulation of microtubule dynamics and organization. Arch Biochem Biophys 2011, 510:83-92.
• [121]Wordeman L, Mitchison TJ: Identification and partial characterization of mitotic centromere-associated kinesin, a kinesin-related protein that associates with centromeres during mitosis. J Cell Biol 1995, 128:95-104.
• [122]Moores CA, Milligan RA: Lucky 13-microtubule depolymerisation by kinesin-13 motors. J Cell Sci 2006, 119:3905-3913.
• [123]Kline-Smith SL, Khodjakov A, Hergert P, Walczak CE: Depletion of centromeric MCAK leads to chromosome congression and segregation defects due to improper kinetochore attachments. Mol Biol Cell 2004, 15:1146-1159.
• [124]Lee T, Langford KJ, Askham JM, Bruning-Richardson A, Morrison EE: MCAK associates with EB1. Oncogene 2008, 27:2494-2500.
• [125]Banks JD, Heald R: Adenomatous polyposis coli associates with the microtubule-destabilizing protein XMCAK. Curr Biol 2004, 14:2033-2038.
• [126]Fan Y, Esmail MA, Ansley SJ, Blacque OE, Boroevich K, Ross AJ, Moore SJ, Badano JL, May-Simera H, Compton DS, Green JS, Lewis RA, van Haelst MM, Parfrey PS, Baillie DL, Beales PL, Katsanis N, Davidson WS, Leroux MR: Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome. Nat Genet 2004, 36:989-993.
• [127]Donaldson JG, Jackson CL: ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat Rev Mol Cell Biol 2011, 12:362-375.
• [128]Etienne-Manneville S: Cdc42--the centre of polarity. J Cell Sci 2004, 117:1291-1300.
• [129]Cau J, Hall A: Cdc42 controls the polarity of the actin and microtubule cytoskeletons through two distinct signal transduction pathways. J Cell Sci 2005, 118:2579-2587.
• [130]Schlessinger K, McManus EJ, Hall A: Cdc42 and noncanonical Wnt signal transduction pathways cooperate to promote cell polarity. J Cell Biol 2007, 178:355-361.
• [131]Mitsushima M, Toyoshima F, Nishida E: Dual role of Cdc42 in spindle orientation control of adherent cells. Mol Cell Biol 2009, 29:2816-2827.
• [132]Balklava Z, Pant S, Fares H, Grant BD: Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic. Nat Cell Biol 2007, 9:1066-1073.
• [133]Zhang X, Zhu J, Yang GY, Wang QJ, Qian L, Chen YM, Chen F, Tao Y, Hu HS, Wang T, Luo ZG: Dishevelled promotes axon differentiation by regulating atypical protein kinase C. Nat Cell Biol 2007, 9:743-754.
• [134]Sfakianos J, Togawa A, Maday S, Hull M, Pypaert M, Cantley L, Toomre D, Mellman I: Par3 functions in the biogenesis of the primary cilium in polarized epithelial cells. J Cell Biol 2007, 179:1133-1140.
• [135]Fan S, Hurd TW, Liu CJ, Straight SW, Weimbs T, Hurd EA, Domino SE, Margolis B: Polarity proteins control ciliogenesis via kinesin motor interactions. Curr Biol 2004, 14:1451-1461.
• [136]Zuo X, Fogelgren B, Lipschutz JH: The small GTPase Cdc42 is necessary for primary ciliogenesis in renal tubular epithelial cells. J Biol Chem 2011, 286:22469-22477.
• [137]Wiens CJ, Tong Y, Esmail MA, Oh E, Gerdes JM, Wang J, Tempel W, Rattner JB, Katsanis N, Park HW, Leroux MR: Bardet-Biedl syndrome-associated small GTPase ARL6 (BBS3) functions at or near the ciliary gate and modulates Wnt signaling. J Biol Chem 2010, 285:16218-16230.
• [138]Hu J, Wittekind SG, Barr MM: STAM and Hrs down-regulate ciliary TRP receptors. Mol Biol Cell 2007, 18:3277-3289.
• [139]Schermer B, Ghenoiu C, Bartram M, Muller RU, Kotsis F, Hohne M, Kuhn W, Rapka M, Nitschke R, Zentgraf H, Fliegauf M, Orman H, Walz G, Benzing T: The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth. J Cell Biol 2006, 175:547-554.
• [140]Good MC, Zalatan JG, Lim WA: Scaffold proteins: hubs for controlling the flow of cellular information. Science 2011, 332:680-686.
• [141]Murga-Zamalloa CA, Ghosh AK, Patil SB, Reed NA, Chan LS, Davuluri S, Peranen J, Hurd TW, Rachel RA, Khanna H: Accumulation of the Raf-1 kinase inhibitory protein (Rkip) is associated with Cep290-mediated photoreceptor degeneration in ciliopathies. J Biol Chem 2011, 286:28276-28286.
• [142]Sugioka K, Mizumoto K, Sawa H: Wnt regulates spindle asymmetry to generate asymmetric nuclear beta-catenin in C. elegans. Cell 2011, 146:942-954.
• [143]Hsiao YC, Tong ZJ, Westfall JE, Ault JG, Page-McCaw PS, Ferland RJ: Ahi1, whose human ortholog is mutated in Joubert syndrome, is required for Rab8a localization, ciliogenesis and vesicle trafficking. Hum Mol Genet 2009, 18:3926-3941.
• [144]Gray RS, Abitua PB, Wlodarczyk BJ, Szabo-Rogers HL, Blanchard O, Lee I, Weiss GS, Liu KJ, Marcotte EM, Wallingford JB, Finnell RH: The planar cell polarity effector Fuz is essential for targeted membrane trafficking, ciliogenesis and mouse embryonic development. Nat Cell Biol 2009, 11:1225-1232.
• [145]Heydeck W, Zeng H, Liu A: Planar cell polarity effector gene Fuzzy regulates cilia formation and Hedgehog signal transduction in mouse. Dev Dyn 2009, 238:3035-3042.
• [146]Dai D, Zhu H, Wlodarczyk B, Zhang L, Li L, Li AG, Finnell RH, Roop DR, Chen J: Fuz controls the morphogenesis and differentiation of hair follicles through the formation of primary cilia. J Invest Dermatol 2011, 131:302-310.
• [147]Zeng H, Hoover AN, Liu A: PCP effector gene Inturned is an important regulator of cilia formation and embryonic development in mammals. Developmental biology 339:418-428.
• [148]Oishi I, Kawakami Y, Raya A, Callol-Massot C, Izpisua Belmonte JC: Regulation of primary cilia formation and left-right patterning in zebrafish by a noncanonical Wnt signaling mediator, duboraya. Nat Genet 2006, 38:1316-1322.
• [149]Valente EM, Logan CV, Mougou-Zerelli S, Lee JH, Silhavy JL, Brancati F, et al.: Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes. Nat Genet 2010, 42:619-625.
• [150]Tissir F, Qu Y, Montcouquiol M, Zhou L, Komatsu K, Shi D, Fujimori T, Labeau J, Tyteca D, Courtoy P, Poumay Y, Uemura T, Goffinet AM: Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus. Nat Neurosci 2010, 13:700-707.
• [151]Oteiza P, Koppen M, Krieg M, Pulgar E, Farias C, Melo C, Preibisch S, Muller D, Tada M, Hartel S, Heisenberg CP, Concha ML: Planar cell polarity signalling regulates cell adhesion properties in progenitors of the zebrafish laterality organ. Development 2010, 137:3459-3468.