A physiological view of the primary cilium.

The primary cilium, an organelle largely ignored by physiologists, functions both as a mechano-sensor and a chemo-sensor in renal tubular epithelia. This forgotten structure is critically involved in the determination of left-right sidedness during development and is a key factor in the development of polycystic kidney disease, as well as a number of other abnormalities. This review provides an update of our current understanding about the function of primary cilia. Much new information obtained in the past five years has been stimulated, in part, by discoveries of the primary cilium's key role in the genesis of polycystic kidney disease as well as its involvement in determination of left-right axis asymmetry. Here we focus on the various functions of the primary cilium rather than on its role in pathology.

[1]  R. Berliner,et al.  Flow dependence of K+ secretion in cortical distal tubules of the rat. , 1989, The American journal of physiology.

[2]  M. Brueckner,et al.  Cilia are at the heart of vertebrate left-right asymmetry. , 2003, Current opinion in genetics & development.

[3]  W. Dentler,et al.  Flagellar microtubule dynamics in Chlamydomonas: cytochalasin D induces periods of microtubule shortening and elongation; and colchicine induces disassembly of the distal, but not proximal, half of the flagellum , 1992, The Journal of cell biology.

[4]  B. G. Barnes.  Ciliated secretory cells in the pars distalis of the mouse hypophysis. , 1961, Journal of ultrastructure research.

[5]  K. Spring,et al.  Removal of the MDCK Cell Primary Cilium Abolishes Flow Sensing , 2003, The Journal of Membrane Biology.

[6]  J. Rosenbaum,et al.  Assembly of chick brain tubulin onto flagellar microtubules from Chlamydomonas and sea urchin sperm. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[7]  T. Strachan,et al.  Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle. , 2002, Human molecular genetics.

[8]  K. W. Zimmermann,et al.  Beiträge zur Kenntniss einiger Drüsen und Epithelien , 1898 .

[9]  B. Alberts,et al.  Identification of microtubule-associated proteins in the centrosome, spindle, and kinetochore of the early Drosophila embryo , 1989, The Journal of cell biology.

[10]  J. Rosenbaum,et al.  Polarity of flagellar assembly in Chlamydomonas , 1992, The Journal of cell biology.

[11]  S. Somlo,et al.  Polycystin-2 is an intracellular calcium release channel , 2002, Nature Cell Biology.

[12]  P. Niederer,et al.  Experimental elucidation of mechanical load-induced fluid flow and its potential role in bone metabolism and functional adaptation. , 1998, The American journal of the medical sciences.

[13]  P. Niederer,et al.  In vivo demonstration of load-induced fluid flow in the rat tibia and its potential implications for processes associated with functional adaptation. , 2000, The Journal of experimental biology.

[14]  J. Frøkiaer,et al.  Bending the Primary Cilium Opens Ca2+-sensitive Intermediate-Conductance K+ Channels in MDCK Cells , 2003, The Journal of Membrane Biology.

[15]  D. Hall,et al.  The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway , 2001, Current Biology.

[16]  C. Bugg,et al.  Polaris, a protein disrupted in orpk mutant mice, is required for assembly of renal cilium. , 2002, American journal of physiology. Renal physiology.

[17]  J. Praetorius,et al.  Specific lectins map the distribution of fibronectin and beta 1-integrin on living MDCK cells. , 2002, Experimental cell research.

[18]  N. Hirokawa,et al.  Left-Right Asymmetry and Kinesin Superfamily Protein KIF3A: New Insights in Determination of Laterality and Mesoderm Induction by kif3A− /− Mice Analysis , 1999, The Journal of cell biology.

[19]  L. Guay-Woodford,et al.  The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. , 2002, Journal of the American Society of Nephrology : JASN.

[20]  J. Scholey.  Kinesin-II, a membrane traffic motor in axons, axonemes, and spindles , 1996, The Journal of cell biology.

[21]  Jing Zhou,et al.  Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells , 2003, Nature Genetics.

[22]  J. Frøkiaer,et al.  Beta1-integrins in the primary cilium of MDCK cells potentiate fibronectin-induced Ca2+ signaling. , 2004, American journal of physiology. Renal physiology.

[23]  D. Wheatley,et al.  CONFOCAL ANALYSIS OF PRIMARY CILIA STRUCTURE AND COLOCALIZATION WITH THE GOLGI APPARATUS IN CHONDROCYTES AND AORTIC SMOOTH MUSCLE CELLS , 1997, Cell biology international.

[24]  D. Wheatley,et al.  Length control of primary cilia: analysis of monociliate and multiciliate PtK1 cells , 2000, Biology of the cell.

[25]  J. Thomas,et al.  The C. elegans homolog of the murine cystic kidney disease gene Tg737 functions in a ciliogenic pathway and is disrupted in osm-5 mutant worms. , 2001, Development.

[26]  J. Martín,et al.  prx-1 functions cooperatively with another paired-related homeobox gene, prx-2, to maintain cell fates within the craniofacial mesenchyme. , 1999, Development.

[27]  S. Schulz,et al.  Selective targeting of somatostatin receptor 3 to neuronal cilia , 1999, Neuroscience.

[28]  Y. Li,et al.  Interactions of mechanotransduction pathways. , 2003, Biorheology.

[29]  J. Whitfield.  Primary cilium—is it an osteocyte's strain‐sensing flowmeter? , 2003, Journal of cellular biochemistry.

[30]  D. Supp,et al.  Targeted deletion of the ATP binding domain of left-right dynein confirms its role in specifying development of left-right asymmetries. , 1999, Development.

[31]  G. Pazour,et al.  A Dynein Light Chain Is Essential for the Retrograde Particle Movement of Intraflagellar Transport (IFT) , 1998, The Journal of cell biology.

[32]  Sheldon Weinbaum,et al.  Effect of flow and stretch on the [Ca2+]i response of principal and intercalated cells in cortical collecting duct. , 2003, American journal of physiology. Renal physiology.

[33]  C. Rieder,et al.  The occurrence and structure of primary cilia in a subline of Potorous tridactylus. , 1979, Experimental cell research.

[34]  H. Schwark,et al.  Neuronal primary cilia: a review , 2004, Cell biology international.

[35]  P. Beech,et al.  The Chlamydomonas kinesin-like protein FLA10 is involved in motility associated with the flagellar membrane , 1995, The Journal of cell biology.

[36]  A. A. Aughsteen.  The ultrastructure of primary cilia in the endocrine and excretory duct cells of the pancreas of mice and rats. , 2001, European journal of morphology.

[37]  Heikki Vaananen,et al.  Primary cilia of human endothelial cells disassemble under laminar shear stress , 2004, The Journal of cell biology.

[38]  O. Hamill,et al.  Brefeldin A Block of Integrin-dependent Mechanosensitive ATP Release from Xenopus Oocytes Reveals a Novel Mechanism of Mechanotransduction* , 2001, The Journal of Biological Chemistry.

[39]  N Wang,et al.  Mechanical interactions among cytoskeletal filaments. , 1998, Hypertension.

[40]  Y. Saijoh,et al.  Determination of left–right patterning of the mouse embryo by artificial nodal flow , 2002, Nature.

[41]  G. Pazour,et al.  Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease , 2002, Current Biology.

[42]  Jing Zhou,et al.  Polycystins and mechanosensation in renal and nodal cilia , 2004, BioEssays : news and reviews in molecular, cellular and developmental biology.

[43]  J. Apfeld,et al.  Regulation of lifespan by sensory perception in Caenorhabditis elegans , 1999, Nature.

[44]  D. Wheatley.  Primary cilia in normal and pathological tissues. , 1995, Pathobiology : journal of immunopathology, molecular and cellular biology.

[45]  L. Satlin,et al.  Flow-dependent K+ secretion in the cortical collecting duct is mediated by a maxi-K channel. , 2001, American journal of physiology. Renal physiology.

[46]  E. A. Schwartz,et al.  Analysis and modeling of the primary cilium bending response to fluid shear. , 1997, The American journal of physiology.

[47]  M. Hamon,et al.  Localization of 5-HT6 receptors at the plasma membrane of neuronal cilia in the rat brain , 2000, Brain Research.

[48]  A. Kocharyan,et al.  Leptin‐Target Neurones of the Rat Hypothalamus Express Somatostatin Receptors , 2003, Journal of neuroendocrinology.

[49]  Y. Saijoh,et al.  The left-right determinant Inversin is a component of node monocilia and other 9+0 cilia , 2003, Development.

[50]  C. Montell.  Physiology, Phylogeny, and Functions of the TRP Superfamily of Cation Channels , 2001, Science's STKE.

[51]  G. Pazour,et al.  Chlamydomonas IFT88 and Its Mouse Homologue, Polycystic Kidney Disease Gene Tg737, Are Required for Assembly of Cilia and Flagella , 2000, The Journal of cell biology.

[52]  G. Borisy,et al.  Structural polarity and directional growth of microtubules of Chlamydomonas flagella. , 1974, Journal of molecular biology.

[53]  Randle W. Ware,et al.  The nerve ring of the nematode Caenorhabditis elegans: Sensory input and motor output , 1975 .

[54]  Theo H Smit,et al.  A Case for Strain‐Induced Fluid Flow as a Regulator of BMU‐Coupling and Osteonal Alignment , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[55]  M. Breuning,et al.  Altered distribution and co-localization of polycystin-2 with polycystin-1 in MDCK cells after wounding stress. , 2004, Experimental cell research.

[56]  K. R. Spring,et al.  Bending the MDCK Cell Primary Cilium Increases Intracellular Calcium , 2001, The Journal of Membrane Biology.

[57]  N. Hirokawa,et al.  Abnormal nodal flow precedes situs inversus in iv and inv mice. , 1999, Molecular cell.

[58]  J. Rosenbaum,et al.  FLAGELLAR REGENERATION IN PROTOZOAN FLAGELLATES , 1967, The Journal of cell biology.

[59]  H. Goodson,et al.  Molecular phylogeny of the kinesin family of microtubule motor proteins. , 1994, Journal of cell science.

[60]  B. Dworniczak,et al.  The Ion Channel Polycystin-2 Is Required for Left-Right Axis Determination in Mice , 2002, Current Biology.

[61]  L. Goldstein,et al.  Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-II. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[62]  S. Bowser,et al.  Ultrastructural, tomographic and confocal imaging of the chondrocyte primary cilium in situ , 2004, Cell biology international.

[63]  P. Beech,et al.  Chlamydomonas Kinesin-II–dependent Intraflagellar Transport (IFT): IFT Particles Contain Proteins Required for Ciliary Assembly in Caenorhabditis elegans Sensory Neurons , 1998, The Journal of cell biology.

[64]  T. Begenisich,et al.  Regulation of fluid and electrolyte secretion in salivary gland acinar cells. , 2005, Annual review of physiology.

[65]  G. Piperno,et al.  Transport of a novel complex in the cytoplasmic matrix of Chlamydomonas flagella. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[66]  K. Kozminski,et al.  A motility in the eukaryotic flagellum unrelated to flagellar beating. , 1993, Proceedings of the National Academy of Sciences of the United States of America.