The genes, proteins and structure of cilia, flagella and their parent organelles, centrioles and basal bodies, have been highly conserved from protists and lower plants to humans (but lost in fungi and higher plants). Pathologies involving cilia (and flagella) present an astonishing diversity of human diseases and developmental disorders affecting virtually every organ in the embryo and adult body, including anosmia, brain development & disease, neurological abnormalities, obesity, respiratory diseases, polycystic kidney disease, retinitis pigmentosis, situs inversus (reversal of left-right body axis, heart on the right side), and male infertility. The importance of cilia stems from their dual, motile and sensory functions. The universal feature of cilia is their 9-fold arrangement of doublet MTs, whose complexity revolves around the A-tubule. The nature of this complexity is not understood but it involves a specialized region of 3-protofilaments that contain a filament composed of the proteins tektins and epilepsy-associated proteins, which my laboratory discovered and characterized (see Selected Publications). My laboratory is focused on the hypothesis concerning tektin function and includes several concepts: (i) That tektin filaments stabilize doublet MTs, even during tubulin-turnover and motility; (ii) that they act as molecular rulers, determining the periodic binding sites of the effector molecules; and (iii) that they interact functionally with the effector molecules, forming load-bearing cables in A-tubules, critical for ciliary/flagellar propulsion. Research in the lab involves protein chemistry and structural analysis by electron microscopy and x-ray diffraction.
Selected Publications (Pubmed Search)
Linck, R., Fu, X., Lin, J., Ouch, C., Schefter, A., Steffen, W., Warren, P., and Nicastro, D. (2014). Insights into the Structure and Function of Ciliary and Flagellar Doublet Microtubules: TEKTINS, Ca2+-BINDING PROTEINS, AND STABLE. Journal of Biological Chemistry. 289, 17427. DOI: 10.1074/jbc.M114.568949
Linck, R.W., and Stephens, R.E. (2007) Functional Protofilament Numbering of Ciliary, Flagellar and Centriolar Microtubules. Cell Motil. Cytoskeleton 64, 489-495.
Setter, P.W., Malvey-Dorn E., Steffen W. Stephens R.E., and Linck R.W. (2006) Tektin interactions and a model for molecular functions. Exp. Cell Res. 312, 2880-2896.
Ikeda, K., Brown, J.A., Yagi, T., Norrander, J.M., Hirono, M., Eccleston, E.D., Kamiya, R., and Linck, R.W. (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, 7725-7734.
Linck, R.W. (2000) Cilia and Flagella. http://www.els.net
Norrander, J., Larsson, M., Ståhl, S., Höög, C., and Linck, R. (1998) Expression of ciliary tektins in brain and sensory development. J. Neurosci. 18, 8912-8918.