description): This research will define the molecular template of ciliary and flagellar microtubules. These organelles are essential for the development and survival of species from protozoa to humans, where they function in the propulsion of protozoa and sperm, and in epithelial transport of embryonic morphogens, cerebrospinal fluid, and tracheal and oviduct contents. Cilia also function in the chemo-/mechano-receptors, retinal photoreceptors, acoustico-vestibular systems, and olfactory neurons. Cilia, flagella, and their parent organelles, centrioles and basal bodies are constructed of an evolutionarily axoneme of doublet and triplet microtubules: these tubules contain specialized sets of protofilaments, termed ribbons, composed of tektins, tubulin and other proteins. Based on the molecular details of tektins and ribbons, the applicant proposes the original hypothesis that this ribbon structure forms a fundamental template for the assembly of centrioles, basal bodies, cilia and flagella. This hypothesis will be tested using the biflagellate Chlamydomonas reinhardtii system, in which the functions of ribbon proteins will be analyzed by a combined application of genetics, protein chemistry, and structural analysis of mutants. One gene/protein, RIB43a/rib43a with homologues in trypanosomes and humans is already under analysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM035648-16
Application #
6519198
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Deatherage, James F
Project Start
1985-02-01
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
16
Fiscal Year
2002
Total Cost
$288,460
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Genetics
Type
Schools of Arts and Sciences
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Linck, Richard W; Chemes, Hector; Albertini, David F (2016) The axoneme: the propulsive engine of spermatozoa and cilia and associated ciliopathies leading to infertility. J Assist Reprod Genet 33:141-56
Setter, Peter W; Malvey-Dorn, Erika; Steffen, Walter et al. (2006) Tektin interactions and a model for molecular functions. Exp Cell Res 312:2880-96
Ikeda, Kazuho; Brown, Jennifer A; Yagi, Toshiki et al. (2003) Rib72, a conserved protein associated with the ribbon compartment of flagellar A-microtubules and potentially involved in the linkage between outer doublet microtubules. J Biol Chem 278:7725-34
Linck, Richard W; Norrander, Jan M (2003) Protofilament ribbon compartments of ciliary and flagellar microtubules. Protist 154:299-311
Norrander, J M; deCathelineau, A M; Brown, J A et al. (2000) The Rib43a protein is associated with forming the specialized protofilament ribbons of flagellar microtubules in Chlamydomonas. Mol Biol Cell 11:201-15
Hinchcliffe, E H; Linck, R W (1998) Two proteins isolated from sea urchin sperm flagella: structural components common to the stable microtubules of axonemes and centrioles. J Cell Sci 111 ( Pt 5):585-95
Norrander, J; Larsson, M; Stahl, S et al. (1998) Expression of ciliary tektins in brain and sensory development. J Neurosci 18:8912-8
Norrander, J M; Perrone, C A; Amos, L A et al. (1996) Structural comparison of tektins and evidence for their determination of complex spacings in flagellar microtubules. J Mol Biol 257:385-97
Norrander, J M; Linck, R W; Stephens, R E (1995) Transcriptional control of tektin A mRNA correlates with cilia development and length determination during sea urchin embryogenesis. Development 121:1615-23
Nojima, D; Linck, R W; Egelman, E H (1995) At least one of the protofilaments in flagellar microtubules is not composed of tubulin. Curr Biol 5:158-67

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