Signaling through the Primary Cilium

被引:344
作者
Wheway, Gabrielle [1 ]
Nazlamova, Liliya [1 ]
Hancock, John T. [1 ]
机构
[1] Univ West England, Fac Hlth & Appl Sci, Ctr Res Biosci, Dept Appl Sci, Bristol, Avon, England
基金
英国惠康基金;
关键词
cell signaling; primary cilium; ciliopathies; Hedgehog; development; developmental disorders; INTRAFLAGELLAR TRANSPORT PROTEIN; KIDNEY-SPECIFIC INACTIVATION; SONIC-HEDGEHOG; MOUSE MODEL; BASAL BODY; CILIARY LOCALIZATION; RETINAL DEGENERATION; NEURONAL CILIA; CELL POLARITY; NOTCH;
D O I
10.3389/fcell.2018.00008
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The presence of single, non-motile "primary" cilia on the surface of epithelial cells has been well described since the 1960s. However, for decades these organelles were believed to be vestigial, with no remaining function, having lost their motility. It wasn't until 2003, with the discovery that proteins responsible for transport along the primary cilium are essential for hedgehog signaling in mice, that the fundamental importance of primary cilia in signal transduction was realized. Little more than a decade later, it is now clear that the vast majority of signaling pathways in vertebrates function through the primary cilium. This has led to the adoption of the term "the cells's antenna" as a description for the primary cilium. Primary cilia are particularly important during development, playing fundamental roles in embryonic patterning and organogenesis, with a suite of inherited developmental disorders known as the "ciliopathies" resulting from mutations in genes encoding cilia proteins. This review summarizes our current understanding of the role of these fascinating organelles in a wide range of signaling pathways.
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页数:13
相关论文
共 121 条
[1]   Variable expressivity of ciliopathy neurological phenotypes that encompass MeckelGruber syndrome and Joubert syndrome is caused by complex de-regulated ciliogenesis, Shh and Wnt signalling defects [J].
Abdelhamed, Zakia A. ;
Wheway, Gabrielle ;
Szymanska, Katarzyna ;
Natarajan, Subaashini ;
Toomes, Carmel ;
Inglehearn, Chris ;
Johnson, Colin A. .
HUMAN MOLECULAR GENETICS, 2013, 22 (07) :1358-1372
[2]   A meckelinfilamin A interaction mediates ciliogenesis [J].
Adams, Matthew ;
Simms, Roslyn J. ;
Abdelhamed, Zakia ;
Dawe, Helen R. ;
Szymanska, Katarzyna ;
Logan, Clare V. ;
Wheway, Gabrielle ;
Pitt, Eva ;
Gull, Keith ;
Knowles, Margaret A. ;
Blair, Edward ;
Cross, Sally H. ;
Sayer, John A. ;
Johnson, Colin A. .
HUMAN MOLECULAR GENETICS, 2012, 21 (06) :1272-1286
[3]   Development and distribution of neuronal cilia in mouse neocortex [J].
Arellano, Jon I. ;
Guadiana, Sarah M. ;
Breunig, Joshua J. ;
Rakic, Pasko ;
Sarkisian, Matthew R. .
JOURNAL OF COMPARATIVE NEUROLOGY, 2012, 520 (04) :848-873
[4]  
Basten Sander G, 2013, Cilia, V2, P6, DOI 10.1186/2046-2530-2-6
[5]   IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy [J].
Beales, Philip L. ;
Bland, Elizabeth ;
Tobin, Jonathan L. ;
Bacchelli, Chiara ;
Tuysuz, Beyhan ;
Hill, Josephine ;
Rix, Suzanne ;
Pearson, Chad G. ;
Kai, Masatake ;
Hartley, Jane ;
Johnson, Colin ;
Irving, Melita ;
Elcioglu, Nursel ;
Winey, Mark ;
Tada, Masazumi ;
Scambler, Peter J. .
NATURE GENETICS, 2007, 39 (06) :727-729
[6]   Bardet-Biedl syndrome proteins are required for the localization of G protein-coupled receptors to primary cilia [J].
Berbari, Nicolas F. ;
Lewis, Jacqueline S. ;
Bishop, Georgia A. ;
Askwith, Candice C. ;
Mykytyn, Kirk .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (11) :4242-4246
[7]   Hippocampal neurons possess primary cilia in culture [J].
Berbari, Nicolas F. ;
Bishop, Georgia A. ;
Askwith, Candice C. ;
Lewis, Jacqueline S. ;
Mykytyn, Kirk .
JOURNAL OF NEUROSCIENCE RESEARCH, 2007, 85 (05) :1095-1100
[8]   Loss of nephrocystin-3 function can cause embryonic lethality, meckel-gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia [J].
Bergmann, Carsten ;
Fliegauf, Manfred ;
Bruechle, Nadina Ortiz ;
Frank, Valeska ;
Olbrich, Heike ;
Kirschner, Jan ;
Schermer, Bernhard ;
Schmedding, Ingolf ;
Kispert, Andreas ;
Kraenzlin, Bettina ;
Nuernberg, Gudrun ;
Becker, Christian ;
Grimm, Tiemo ;
Girschick, Gundula ;
Lynch, Sally A. ;
Kelehan, Peter ;
Senderek, Jan ;
Neuhaus, Thomas J. ;
Stallmach, Thomas ;
Zentgraf, Hanswalter ;
Nuernberg, Peter ;
Gretz, Norbert ;
Lo, Cecilia ;
Lienkamp, Soeren ;
Schaefer, Tobias ;
Walz, Gerd ;
Benzing, Thomas ;
Zerres, Klaus ;
Omran, Heymut .
AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 82 (04) :959-970
[9]   Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies [J].
Bielas, Stephanie L. ;
Silhavy, Jennifer L. ;
Brancati, Francesco ;
Kisseleva, Marina V. ;
Al-Gazali, Lihadh ;
Laszlo Sztriha ;
Bayoumi, Riad A. ;
Zaki, Maha S. ;
Abdel-Aleem, Alice ;
Rosti, Rasim Ozgur ;
Kayserili, Hulya ;
Swistun, Dominika ;
Scott, Lesley C. ;
Bertini, Enrico ;
Boltshauser, Eugen ;
Fazzi, Elisa ;
Travaglini, Lorena ;
Field, Seth J. ;
Gayral, Stephanie ;
Jacoby, Monique ;
Schurmans, Stephane ;
Dallapiccola, Bruno ;
Majerus, Philip W. ;
Valente, Enza Maria ;
Gleeson, Joseph G. .
NATURE GENETICS, 2009, 41 (09) :1032-U108
[10]   Primary cilia regulate mTORC1 activity and cell size through Lkb1 [J].
Boehlke, Christopher ;
Kotsis, Fruzsina ;
Patel, Vishal ;
Braeg, Simone ;
Voelker, Henriette ;
Bredt, Saskia ;
Beyer, Theresa ;
Janusch, Heike ;
Hamann, Christoph ;
Goedel, Markus ;
Mueller, Klaus ;
Herbst, Martin ;
Hornung, Miriam ;
Doerken, Mara ;
Koettgen, Michael ;
Nitschke, Roland ;
Igarashi, Peter ;
Walz, Gerd ;
Kuehn, E. Wolfgang .
NATURE CELL BIOLOGY, 2010, 12 (11) :1115-U126