Review

The Roles of Primary cilia in Polycystic Kidney Disease

  • Received: 05 October 2013 Accepted: 03 December 2013 Published: 13 December 2014
  • Autosomal dominant polycystic kidney disease (ADPKD) is an inherited genetic disorder that results in progressive renal cyst formation with ultimate loss of renal function and other systemic disorders. These systemic disorders include abnormalities in cardiovascular, portal, pancreatic and gastrointestinal systems. ADPKD is considered to be among the ciliopathy diseases due to the association with abnormal primary cilia function. In order to understand the full course of primary cilia and its association with ADPKD, the structure, functions and role of primary cilia have been meticulously investigated. As a result, the focus on primary cilia has emerged to support the vital roles of primary cilia in ADPKD. The primary cilia have been shown to have not only a mechanosensory function but also a chemosensory function. Both structural and functional defects in primary cilia result in cystic kidney disease and vascular hypertension. Thus, the mechanosenory and chemosensory functions will be analyzed in regards to ADPKD.

    Citation: Sarmed H. Kathem, Ashraf M. Mohieldin, Surya M. Nauli. The Roles of Primary cilia in Polycystic Kidney Disease[J]. AIMS Molecular Science, 2014, 1(1): 27-46. doi: 10.3934/molsci.2013.1.27

    Related Papers:

  • Autosomal dominant polycystic kidney disease (ADPKD) is an inherited genetic disorder that results in progressive renal cyst formation with ultimate loss of renal function and other systemic disorders. These systemic disorders include abnormalities in cardiovascular, portal, pancreatic and gastrointestinal systems. ADPKD is considered to be among the ciliopathy diseases due to the association with abnormal primary cilia function. In order to understand the full course of primary cilia and its association with ADPKD, the structure, functions and role of primary cilia have been meticulously investigated. As a result, the focus on primary cilia has emerged to support the vital roles of primary cilia in ADPKD. The primary cilia have been shown to have not only a mechanosensory function but also a chemosensory function. Both structural and functional defects in primary cilia result in cystic kidney disease and vascular hypertension. Thus, the mechanosenory and chemosensory functions will be analyzed in regards to ADPKD.


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    [1] Lentine KL, Xiao H, Machnicki G, et al. (2010) Renal function and healthcare costs in patients with polycystic kidney disease. Clin J Am Soc Nephrol 5: 1471-1479. doi: 10.2215/CJN.00780110
    [2] Torres VE, Harris PC (2009) Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 76: 149-168. doi: 10.1038/ki.2009.128
    [3] Grantham JJ, Torres VE, Chapman AB, et al. (2006) Volume progression in polycystic kidney disease. N Engl J Med 354: 2122-2130. doi: 10.1056/NEJMoa054341
    [4] Churchill DN, Bear JC, Morgan J, et al. (1984) Prognosis of adult onset polycystic kidney disease re-evaluated. Kidney Int 26: 190-193. doi: 10.1038/ki.1984.154
    [5] Dell KM (2011) The spectrum of polycystic kidney disease in children. Adv Chronic Kidney Dis 18: 339-347. doi: 10.1053/j.ackd.2011.05.001
    [6] Romao EA, Moyses Neto M, Teixeira SR, et al. (2006) Renal and extrarenal manifestations of autosomal dominant polycystic kidney disease. Braz J Med Biol Res 39: 533-538. doi: 10.1590/S0100-879X2006000400014
    [7] Gabow PA (1993) Autosomal dominant polycystic kidney disease. N Engl J Med 329: 332-342. doi: 10.1056/NEJM199307293290508
    [8] Huston J, 3rd, Torres VE, Sulivan PP, et al. (1993) Value of magnetic resonance angiography for the detection of intracranial aneurysms in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 3: 1871-1877.
    [9] Abdul-Majeed S, Nauli SM (2011) Polycystic diseases in visceral organs. Obstet Gynecol Int 2011: 609370.
    [10] Ratnam S, Nauli SM (2010) Hypertension in Autosomal Dominant Polycystic Kidney Disease: A Clinical and Basic Science Perspective. Int J Nephrol Urol 2: 294-308.
    [11] Zimmermann K (1898) Beiträge zur Kenntnis einiger Drüsen und Epithelien. Arch MikroskopAnat 52: 552-706. doi: 10.1007/BF02975837
    [12] Nauli SM, Haymour HS, AbouAlaiwi WA, et al. (2011) Chapter 14: Primary Cilia are Mechanosensory Organelles in Vestibular Tissues. Mechanosensitivity and Mechanotransduction: ISBN: 978-990-481-9880-9881.
    [13] Jin X, Mohieldin AM, Muntean BS, et al. (2013) Cilioplasm is a cellular compartment for calcium signaling in response to mechanical and chemical stimuli. Cell Mol Life Sci.
    [14] Garcia-Gonzalo FR, Reiter JF (2012) Scoring a backstage pass: mechanisms of ciliogenesis and ciliary access. J Cell Biol 197: 697-709. doi: 10.1083/jcb.201111146
    [15] Gherman A, Davis EE, Katsanis N (2006) The ciliary proteome database: an integrated community resource for the genetic and functional dissection of cilia. Nat Genet 38: 961-962. doi: 10.1038/ng0906-961
    [16] Nauli SM, Jin X, Hierck BP (2011) The mechanosensory role of primary cilia in vascular hypertension. Int J Vasc Med 2011: 376281.
    [17] Abdul-Majeed S, Nauli SM (2011) Calcium-mediated mechanisms of cystic expansion. Biochim Biophys Acta 1812: 1281-1290. doi: 10.1016/j.bbadis.2010.09.016
    [18] Nauli SM, Zhou J (2004) Polycystins and mechanosensation in renal and nodal cilia. Bioessays 26: 844-856. doi: 10.1002/bies.20069
    [19] Satir P, Pedersen LB, Christensen ST (2010) The primary cilium at a glance. J Cell Sci 123:499-503. doi: 10.1242/jcs.050377
    [20] Wood CR, Huang K, Diener DR, et al. (2013) The cilium secretes bioactive ectosomes. Curr Biol 23: 906-911. doi: 10.1016/j.cub.2013.04.019
    [21] Kaimori JY, Nagasawa Y, Menezes LF, et al. (2007) Polyductin undergoes notch-like processing and regulated release from primary cilia. Hum Mol Genet 16: 942-956. doi: 10.1093/hmg/ddm039
    [22] Qian F, Boletta A, Bhunia AK, et al. (2002) Cleavage of polycystin-1 requires the receptor for egg jelly domain and is disrupted by human autosomal-dominant polycystic kidney disease 1-associated mutations. Proc Natl Acad Sci U S A 99: 16981-16986. doi: 10.1073/pnas.252484899
    [23] Tanaka Y, Okada Y, Hirokawa N (2005) FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination. Nature 435:172-177. doi: 10.1038/nature03494
    [24] Hogan MC, Manganelli L, Woollard JR, et al. (2009) Characterization of PKD proteinpositive exosome-like vesicles. J Am Soc Nephrol 20: 278-288. doi: 10.1681/ASN.2008060564
    [25] Praetorius HA, Spring KR (2003) Removal of the MDCK cell primary cilium abolishes flow sensing. J Membr Biol 191: 69-76. doi: 10.1007/s00232-002-1042-4
    [26] Nauli SM, Rossetti S, Kolb RJ, et al. (2006) Loss of polycystin-1 in human cyst-lining epithelia leads to ciliary dysfunction. J Am Soc Nephrol 17: 1015-1025. doi: 10.1681/ASN.2005080830
    [27] Nauli SM, Alenghat FJ, Luo Y, et al. (2003) Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 33: 129-137. doi: 10.1038/ng1076
    [28] AbouAlaiwi WA, Takahashi M, Mell BR, et al. (2009) Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades. Circ Res 104:860-869. doi: 10.1161/CIRCRESAHA.108.192765
    [29] Schwartz EA, Leonard ML, Bizios R, et al. (1997) Analysis and modeling of the primary cilium bending response to fluid shear. Am J Physiol 272: F132-138.
    [30] Downs ME, Nguyen AM, Herzog FA, et al. (2012) An experimental and computational analysis of primary cilia deflection under fluid flow. Comput Methods Biomech Biomed Engin.
    [31] Resnick A, Hopfer U (2008) Mechanical stimulation of primary cilia. Front Biosci 13: 1665-1680. doi: 10.2741/2790
    [32] Rydholm S, Zwartz G, Kowalewski JM, et al. (2010) Mechanical properties of primary cilia regulate the response to fluid flow. Am J Physiol Renal Physiol 298: F1096-1102. doi: 10.1152/ajprenal.00657.2009
    [33] Forman JR, Qamar S, Paci E, et al. (2005) The remarkable mechanical strength of polycystin-1 supports a direct role in mechanotransduction. J Mol Biol 349: 861-871. doi: 10.1016/j.jmb.2005.04.008
    [34] Abdul-Majeed S, Nauli SM (2011) Dopamine receptor type 5 in the primary cilia has dual chemo- and mechano-sensory roles. Hypertension 58: 325-331. doi: 10.1161/HYPERTENSIONAHA.111.172080
    [35] Hamon M, Doucet E, Lefevre K, et al. (1999) Antibodies and antisense oligonucleotide for probing the distribution and putative functions of central 5-HT6 receptors. Neuropsychopharmacology 21: 68S-76S.
    [36] Handel M, Schulz S, Stanarius A, et al. (1999) Selective targeting of somatostatin receptor 3 to neuronal cilia. Neuroscience 89: 909-926. doi: 10.1016/S0306-4522(98)00354-6
    [37] Masyuk AI, Gradilone SA, Banales JM, et al. (2008) Cholangiocyte primary cilia are chemosensory organelles that detect biliary nucleotides via P2Y12 purinergic receptors. Am J Physiol Gastrointest Liver Physiol 295: G725-734. doi: 10.1152/ajpgi.90265.2008
    [38] Berbari NF, Johnson AD, Lewis JS, et al. (2008) Identification of ciliary localization sequences within the third intracellular loop of G protein-coupled receptors. Mol Biol Cell 19:1540-1547. doi: 10.1091/mbc.E07-09-0942
    [39] Rohatgi R, Milenkovic L, Scott MP (2007) Patched1 regulates hedgehog signaling at the primary cilium. Science 317: 372-376. doi: 10.1126/science.1139740
    [40] Corbit KC, Aanstad P, Singla V, et al. (2005) Vertebrate Smoothened functions at the primary cilium. Nature 437: 1018-1021. doi: 10.1038/nature04117
    [41] Kim E, Arnould T, Sellin LK, et al. (1999) The polycystic kidney disease 1 gene product modulates Wnt signaling. J Biol Chem 274: 4947-4953. doi: 10.1074/jbc.274.8.4947
    [42] Schneider L, Clement CA, Teilmann SC, et al. (2005) PDGFRalphaalpha signaling is regulated through the primary cilium in fibroblasts. Curr Biol 15: 1861-1866. doi: 10.1016/j.cub.2005.09.012
    [43] Soetedjo L, Glover DA, Jin H (2013) Targeting of vasoactive intestinal peptide receptor 2, VPAC2, a secretin family G-protein coupled receptor, to primary cilia. Biol Open 2: 686-694. doi: 10.1242/bio.20134747
    [44] Schneider L, Cammer M, Lehman J, et al. (2010) Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts. Cell Physiol Biochem 25: 279-292. doi: 10.1159/000276562
    [45] Jones TJ, Adapala RK, Geldenhuys WJ, et al. (2012) Primary cilia regulates the directional migration and barrier integrity of endothelial cells through the modulation of hsp27 dependent actin cytoskeletal organization. J Cell Physiol 227: 70-76. doi: 10.1002/jcp.22704
    [46] Jones TJ, Nauli SM (2012) Mechanosensory calcium signaling. Adv Exp Med Biol 740: 1001-1015. doi: 10.1007/978-94-007-2888-2_46
    [47] Choi YH, Suzuki A, Hajarnis S, et al. (2011) Polycystin-2 and phosphodiesterase 4C are components of a ciliary A-kinase anchoring protein complex that is disrupted in cystic kidney diseases. Proc Natl Acad Sci U S A 108: 10679-10684. doi: 10.1073/pnas.1016214108
    [48] Green JA, Gu C, Mykytyn K (2012) Heteromerization of ciliary G protein-coupled receptors in the mouse brain. PLoS One 7: e46304. doi: 10.1371/journal.pone.0046304
    [49] Marley A, Choy RW, von Zastrow M (2013) GPR88 reveals a discrete function of primary cilia as selective insulators of GPCR cross-talk. PLoS One 8: e70857. doi: 10.1371/journal.pone.0070857
    [50] Kolb RJ, Nauli SM (2008) Ciliary dysfunction in polycystic kidney disease: an emerging model with polarizing potential. Front Biosci 13: 4451-4466.
    [51] Nims N, Vassmer D, Maser RL (2003) Transmembrane domain analysis of polycystin-1, the product of the polycystic kidney disease-1 (PKD1) gene: evidence for 11 membranespanning domains. Biochemistry 42: 13035-13048. doi: 10.1021/bi035074c
    [52] Scheffers MS, van der Bent P, Prins F, et al. (2000) Polycystin-1, the product of the polycystic kidney disease 1 gene, co-localizes with desmosomes in MDCK cells. Hum Mol Genet 9: 2743-2750. doi: 10.1093/hmg/9.18.2743
    [53] Huan Y, van Adelsberg J (1999) Polycystin-1, the PKD1 gene product, is in a complex containing E-cadherin and the catenins. J Clin Invest 104: 1459-1468. doi: 10.1172/JCI5111
    [54] Yu S, Hackmann K, Gao J, et al. (2007) Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure. Proc Natl Acad Sci U S A 104: 18688-18693. doi: 10.1073/pnas.0708217104
    [55] Low SH, Vasanth S, Larson CH, et al. (2006) Polycystin-1, STAT6, and P100 function in a pathway that transduces ciliary mechanosensation and is activated in polycystic kidney disease. Dev Cell 10: 57-69. doi: 10.1016/j.devcel.2005.12.005
    [56] Chauvet V, Tian X, Husson H, et al. (2004) Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. J Clin Invest 114: 1433-1443. doi: 10.1172/JCI21753
    [57] Lal M, Song X, Pluznick JL, et al. (2008) Polycystin-1 C-terminal tail associates with betacatenin and inhibits canonical Wnt signaling. Hum Mol Genet 17: 3105-3117. doi: 10.1093/hmg/ddn208
    [58] Delmas P, Nauli SM, Li X, et al. (2004) Gating of the polycystin ion channel signaling complex in neurons and kidney cells. FASEB J 18: 740-742.
    [59] Parnell SC, Magenheimer BS, Maser RL, et al. (1998) The polycystic kidney disease-1 protein, polycystin-1, binds and activates heterotrimeric G-proteins in vitro. Biochem Biophys Res Commun 251: 625-631. doi: 10.1006/bbrc.1998.9514
    [60] Parnell SC, Magenheimer BS, Maser RL, et al. (2002) Polycystin-1 activation of c-Jun Nterminal kinase and AP-1 is mediated by heterotrimeric G proteins. J Biol Chem 277: 19566-19572. doi: 10.1074/jbc.M201875200
    [61] Arnould T, Kim E, Tsiokas L, et al. (1998) The polycystic kidney disease 1 gene product mediates protein kinase C alpha-dependent and c-Jun N-terminal kinase-dependent activation of the transcription factor AP-1. J Biol Chem 273: 6013-6018. doi: 10.1074/jbc.273.11.6013
    [62] Le NH, van der Wal A, van der Bent P, et al. (2005) Increased activity of activator protein-1 transcription factor components ATF2, c-Jun, and c-Fos in human and mouse autosomal dominant polycystic kidney disease. J Am Soc Nephrol 16: 2724-2731. doi: 10.1681/ASN.2004110913
    [63] Shaulian E, Karin M (2002) AP-1 as a regulator of cell life and death. Nat Cell Biol 4: E131-136. doi: 10.1038/ncb0502-e131
    [64] Yu W, Kong T, Beaudry S, et al. (2010) Polycystin-1 protein level determines activity of the Galpha12/JNK apoptosis pathway. J Biol Chem 285: 10243-10251. doi: 10.1074/jbc.M109.070821
    [65] Puri S, Magenheimer BS, Maser RL, et al. (2004) Polycystin-1 activates the calcineurin/NFAT (nuclear factor of activated T-cells) signaling pathway. J Biol Chem 279:55455-55464. doi: 10.1074/jbc.M402905200
    [66] Distefano G, Boca M, Rowe I, et al. (2009) Polycystin-1 regulates extracellular signalregulated kinase-dependent phosphorylation of tuberin to control cell size through mTOR and its downstream effectors S6K and 4EBP1. Mol Cell Biol 29: 2359-2371. doi: 10.1128/MCB.01259-08
    [67] Shillingford JM, Murcia NS, Larson CH, et al. (2006) The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc Natl Acad Sci U S A 103: 5466-5471. doi: 10.1073/pnas.0509694103
    [68] Mochizuki T, Wu G, Hayashi T, et al. (1996) PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 272: 1339-1342. doi: 10.1126/science.272.5266.1339
    [69] Cai Y, Maeda Y, Cedzich A, et al. (1999) Identification and characterization of polycystin-2, the PKD2 gene product. J Biol Chem 274: 28557-28565. doi: 10.1074/jbc.274.40.28557
    [70] Hanaoka K, Qian F, Boletta A, et al. (2000) Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. Nature 408: 990-994. doi: 10.1038/35050128
    [71] Qian F, Germino FJ, Cai Y, et al. (1997) PKD1 interacts with PKD2 through a probable coiled-coil domain. Nat Genet 16: 179-183. doi: 10.1038/ng0697-179
    [72] Nauli SM, Jin X, AbouAlaiwi WA, et al. (2013) Non-motile primary cilia as fluid shear stress mechanosensors. Methods Enzymol 525: 1-20. doi: 10.1016/B978-0-12-397944-5.00001-8
    [73] Liu W, Murcia NS, Duan Y, et al. (2005) Mechanoregulation of intracellular Ca2+ concentration is attenuated in collecting duct of monocilium-impaired orpk mice. Am J Physiol Renal Physiol 289: F978-988. doi: 10.1152/ajprenal.00260.2004
    [74] Praetorius HA, Spring KR (2001) Bending the MDCK cell primary cilium increases intracellular calcium. J Membr Biol 184: 71-79. doi: 10.1007/s00232-001-0075-4
    [75] Xu C, Shmukler BE, Nishimura K, et al. (2009) 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 296: F1464-1476. doi: 10.1152/ajprenal.90542.2008
    [76] Li Y, Wright JM, Qian F, et al. (2005) Polycystin 2 interacts with type I inositol 1,4,5- trisphosphate receptor to modulate intracellular Ca2+ signaling. J Biol Chem 280: 41298-41306. doi: 10.1074/jbc.M510082200
    [77] Li Y, Santoso NG, Yu S, et al. (2009) Polycystin-1 interacts with inositol 1,4,5-trisphosphate receptor to modulate intracellular Ca2+ signaling with implications for polycystic kidney disease. J Biol Chem 284: 36431-36441. doi: 10.1074/jbc.M109.068916
    [78] Praetorius HA, Leipziger J (2009) Released nucleotides amplify the cilium-dependent, flowinduced [Ca2+]i response in MDCK cells. Acta Physiol (Oxf) 197: 241-251. doi: 10.1111/j.1748-1716.2009.02002.x
    [79] Praetorius HA, Praetorius J, Nielsen S, et al. (2004) Beta1-integrins in the primary cilium of MDCK cells potentiate fibronectin-induced Ca2+ signaling. Am J Physiol Renal Physiol 287: F969-978. doi: 10.1152/ajprenal.00096.2004
    [80] Eggenschwiler JT, Anderson KV (2007) Cilia and developmental signaling. Annu Rev Cell Dev Biol 23: 345-373. doi: 10.1146/annurev.cellbio.23.090506.123249
    [81] Lum L, Beachy PA (2004) The Hedgehog response network: sensors, switches, and routers. Science 304: 1755-1759. doi: 10.1126/science.1098020
    [82] Mohieldin AM, Upadhyay VS, Ong ACM, et al. (2013) Autosomal Dominant Polycystic Kidney Disease: Pathophysiology and Treatment. Autosomal Dominant Disorders: New Research ISBN: 978-1-62808-761-1: 6x9 - (NBC-R).
    [83] Nauli SM (2011) An ACE inhibitor improves vascular outcomes in a PKD model. Am J Physiol Renal Physiol 301: F958. doi: 10.1152/ajprenal.00489.2011
    [84] Andersson M, Karlsson L, Svensson PA, et al. (2005) Differential global gene expression response patterns of human endothelium exposed to shear stress and intraluminal pressure. J Vasc Res 42: 441-452. doi: 10.1159/000087983
    [85] Masuda H, Zhuang YJ, Singh TM, et al. (1999) Adaptive remodeling of internal elastic lamina and endothelial lining during flow-induced arterial enlargement. Arterioscler Thromb Vasc Biol 19: 2298-2307. doi: 10.1161/01.ATV.19.10.2298
    [86] Pries AR, Secomb TW, Gaehtgens P (1995) Design principles of vascular beds. Circ Res 77:1017-1023. doi: 10.1161/01.RES.77.5.1017
    [87] Ohura N, Yamamoto K, Ichioka S, et al. (2003) Global analysis of shear stress-responsive genes in vascular endothelial cells. J Atheroscler Thromb 10: 304-313. doi: 10.5551/jat.10.304
    [88] Langille BL, Bendeck MP, Keeley FW (1989) Adaptations of carotid arteries of young and mature rabbits to reduced carotid blood flow. Am J Physiol 256: H931-939.
    [89] Langille BL, O'Donnell F (1986) Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science 231: 405-407. doi: 10.1126/science.3941904
    [90] Huang C, Holfeld J, Schaden W, et al. (2013) Mechanotherapy: revisiting physical therapy and recruiting mechanobiology for a new era in medicine. Trends Mol Med 19: 555-564. doi: 10.1016/j.molmed.2013.05.005
    [91] Nauli SM, Kawanabe Y, Kaminski JJ, et al. (2008) Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1. Circulation 117: 1161-1171. doi: 10.1161/CIRCULATIONAHA.107.710111
    [92] Hierck BP, Van der Heiden K, Alkemade FE, et al. (2008) Primary cilia sensitize endothelial cells for fluid shear stress. Dev Dyn 237: 725-735. doi: 10.1002/dvdy.21472
    [93] Wang N, Miao H, Li YS, et al. (2006) Shear stress regulation of Kruppel-like factor 2 expression is flow pattern-specific. Biochem Biophys Res Commun 341: 1244-1251. doi: 10.1016/j.bbrc.2006.01.089
    [94] Boon RA, Horrevoets AJ (2009) Key transcriptional regulators of the vasoprotective effects of shear stress. Hamostaseologie 29: 39-40, 41-33.
    [95] Dekker RJ, van Thienen JV, Rohlena J, et al. (2005) Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes. Am J Pathol 167:609-618. doi: 10.1016/S0002-9440(10)63002-7
    [96] SenBanerjee S, Lin Z, Atkins GB, et al. (2004) KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation. J Exp Med 199: 1305-1315. doi: 10.1084/jem.20031132
    [97] Abdul-Majeed S, Moloney BC, Nauli SM (2012) Mechanisms regulating cilia growth and cilia function in endothelial cells. Cell Mol Life Sci 69: 165-173. doi: 10.1007/s00018-011-0744-0
    [98] Clement DL, Mally S, Stock C, et al. (2013) PDGFRalpha signaling in the primary cilium regulates NHE1-dependent fibroblast migration via coordinated differential activity of MEK1/2-ERK1/2-p90RSK and AKT signaling pathways. J Cell Sci 126: 953-965. doi: 10.1242/jcs.116426
    [99] AbouAlaiwi WA, Ratnam S, Booth RL, et al. (2011) Endothelial cells from humans and mice with polycystic kidney disease are characterized by polyploidy and chromosome segregation defects through survivin down-regulation. Hum Mol Genet 20: 354-367. doi: 10.1093/hmg/ddq470
    [100] AbouAlaiwi WA, Rodriguez I, Nauli SM (2012) Spectral karyotyping to study chromosome abnormalities in humans and mice with polycystic kidney disease. J Vis Exp.
    [101] Aboualaiwi WA, Muntean BS, Ratnam S, et al. (2013) Survivin-Induced Abnormal Ploidy Contributes to Cystic Kidney and Aneurysm Formation. Circulation.
    [102] Zaragoza C, Marquez S, Saura M (2012) Endothelial mechanosensors of shear stress as regulators of atherogenesis. Curr Opin Lipidol 23: 446-452. doi: 10.1097/MOL.0b013e328357e837
    [103] Van der Heiden K, Hierck BP, Krams R, et al. (2008) Endothelial primary cilia in areas of disturbed flow are at the base of atherosclerosis. Atherosclerosis 196: 542-550. doi: 10.1016/j.atherosclerosis.2007.05.030
    [104] Bystrevskaya VB, Lichkun VV, Antonov AS, et al. (1988) An ultrastructural study of centriolar complexes in adult and embryonic human aortic endothelial cells. Tissue Cell 20:493-503. doi: 10.1016/0040-8166(88)90052-3
    [105] Iomini C, Tejada K, Mo W, et al. (2004) Primary cilia of human endothelial cells disassemble under laminar shear stress. J Cell Biol 164: 811-817. doi: 10.1083/jcb.200312133
    [106] Abou Alaiwi WA, Lo ST, Nauli SM (2009) Primary cilia: highly sophisticated biological sensors. Sensors (Basel) 9: 7003-7020. doi: 10.3390/s90907003
    [107] Teilmann SC, Christensen ST (2005) Localization of the angiopoietin receptors Tie-1 and Tie-2 on the primary cilia in the female reproductive organs. Cell Biol Int 29: 340-346. doi: 10.1016/j.cellbi.2005.03.006
    [108] Hazzard TM, Molskness TA, Chaffin CL, et al. (1999) Vascular endothelial growth factor (VEGF) and angiopoietin regulation by gonadotrophin and steroids in macaque granulosa cells during the peri-ovulatory interval. Mol Hum Reprod 5: 1115-1121. doi: 10.1093/molehr/5.12.1115
    [109] Kim I, Kim HG, So JN, et al. (2000) Angiopoietin-1 regulates endothelial cell survival through the phosphatidylinositol 3'-Kinase/Akt signal transduction pathway. Circ Res 86: 24-29. doi: 10.1161/01.RES.86.1.24
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