Cilia and flagella are present in a wide variety of eukaryotic cells. Their disfunction is correlated with respiratory ailments or male sterility. This proposal has the following two long-term objectives: analyze the molecular and structural features of those axonemal components that are essential for the generation of axonemal movement and second, identify the molecular mechanisms of regulation that lead to the formation of specific bending patterns of cilia and flagella. Both objectives will be approached with the analysis of the inner dynein arms, because in vivo these structures are necessary and sufficient to generate both ciliary and flagellar types of movement in the absence of outer dynein arms. The organism used is the unicellular green alga Chlamydomonas reinhardtii. This organism allows for the analysis of the axoneme by a combination of approaches including genetics, electron microscopy and biochemical procedures. The comparison of Chlamydomonas wild-type axonemes with mutant axonemes lacking the outer dynein arms or part of the inner arms forms the basis of many experimental procedures outlined in this proposal. The comparison of inner dynein arms prepared from motile flagella with those from nonmotile flagella and analysis of defective inner arms in mutant axonemes, will be adopted to explain the function of the posttranslational modification of inner arm heavy chains. On this basis the long-term objective will be approached with the following specific aims: 1. complete the characterization of the structure and molecular composition of all forms of inner dynein arms present in Chlamydomonas axonemes; 2. develop a detailed analysis of the structures and the modifications of inner arm heavy chains and determine whether the modification of heavy chains is part of mechanism controlling axonemal motility; 3. characterize the axonemal components whose function is correlated with the restoration of flagellar activity of radial spoke-defective mutants; 4. determine whether axonemal actin and caltractin directly are involved in those changes of inner dynein arm activity that occur when Chlamydomonas axonemes pass from the ciliary to the flagellar type of motion.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mount Sinai School of Medicine
Schools of Medicine
New York
United States
Zip Code
Iomini, Carlo; Li, Linya; Mo, Wenjun et al. (2006) Two flagellar genes, AGG2 and AGG3, mediate orientation to light in Chlamydomonas. Curr Biol 16:1147-53
Iomini, Carlo; Tejada, Karla; Mo, Wenjun et al. (2004) Primary cilia of human endothelial cells disassemble under laminar shear stress. J Cell Biol 164:811-7
Iomini, C; Babaev-Khaimov, V; Sassaroli, M et al. (2001) Protein particles in Chlamydomonas flagella undergo a transport cycle consisting of four phases. J Cell Biol 153:13-24
Piperno, G; Siuda, E; Henderson, S et al. (1998) Distinct mutants of retrograde intraflagellar transport (IFT) share similar morphological and molecular defects. J Cell Biol 143:1591-601
Piperno, G; Mead, K (1997) Transport of a novel complex in the cytoplasmic matrix of Chlamydomonas flagella. Proc Natl Acad Sci U S A 94:4457-62
Piperno, G; Mead, K; Henderson, S (1996) Inner dynein arms but not outer dynein arms require the activity of kinesin homologue protein KHP1(FLA10) to reach the distal part of flagella in Chlamydomonas. J Cell Biol 133:371-9
LeDizet, M; Piperno, G (1995) ida4-1, ida4-2, and ida4-3 are intron splicing mutations affecting the locus encoding p28, a light chain of Chlamydomonas axonemal inner dynein arms. Mol Biol Cell 6:713-23
LeDizet, M; Piperno, G (1995) The light chain p28 associates with a subset of inner dynein arm heavy chains in Chlamydomonas axonemes. Mol Biol Cell 6:697-711
Piperno, G; Mead, K; LeDizet, M et al. (1994) Mutations in the ""dynein regulatory complex"" alter the ATP-insensitive binding sites for inner arm dyneins in Chlamydomonas axonemes. J Cell Biol 125:1109-17
Piperno, G; Mead, K; Shestak, W (1992) The inner dynein arms I2 interact with a ""dynein regulatory complex"" in Chlamydomonas flagella. J Cell Biol 118:1455-63

Showing the most recent 10 out of 11 publications