The long term goal of the proposed research is to understand the molecular mechanisms that regulate the assembly, targeting and activity of the dynein family of motor proteins. The investigators laboratory has identified several new genes that are involved in the assembly of the dyein arms in Chlamydomonas. They propose to further characterize these genes and gene products to identify the components that interact to assemble a dyein motor complex and position it correctly inside the cell. The propose to: 1) identify the dyein heavy chain (Dhc) domains required form complex; 2) identify the components that interact with the Dhc to promote complex assembly; and 3) to characterize novel components that regulate the assembly of inner arm dyneins.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM055667-03
Application #
2900901
Study Section
Biological Sciences 2 (BIOL)
Project Start
1997-04-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Bower, Raqual; Tritschler, Douglas; Mills, Kristyn VanderWaal et al. (2018) DRC2/CCDC65 is a central hub for assembly of the nexin-dynein regulatory complex and other regulators of ciliary and flagellar motility. Mol Biol Cell 29:137-153
Chien, Alexander; Shih, Sheng Min; Bower, Raqual et al. (2017) Dynamics of the IFT machinery at the ciliary tip. Elife 6:
Alford, Lea M; Stoddard, Daniel; Li, Jennifer H et al. (2016) The nexin link and B-tubule glutamylation maintain the alignment of outer doublets in the ciliary axoneme. Cytoskeleton (Hoboken) 73:331-40
Lewis, Wesley R; Malarkey, Erik B; Tritschler, Douglas et al. (2016) Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease. PLoS Genet 12:e1006220
Reck, Jaimee; Schauer, Alexandria M; VanderWaal Mills, Kristyn et al. (2016) The role of the dynein light intermediate chain in retrograde IFT and flagellar function in Chlamydomonas. Mol Biol Cell 27:2404-22
Song, Kangkang; Awata, Junya; Tritschler, Douglas et al. (2015) In situ localization of N and C termini of subunits of the flagellar nexin-dynein regulatory complex (N-DRC) using SNAP tag and cryo-electron tomography. J Biol Chem 290:5341-53
Wren, Kathryne N; Craft, Julie M; Tritschler, Douglas et al. (2013) A differential cargo-loading model of ciliary length regulation by IFT. Curr Biol 23:2463-71
Bower, Raqual; Tritschler, Douglas; Vanderwaal, Kristyn et al. (2013) The N-DRC forms a conserved biochemical complex that maintains outer doublet alignment and limits microtubule sliding in motile axonemes. Mol Biol Cell 24:1134-52
Wirschell, Maureen; Olbrich, Heike; Werner, Claudius et al. (2013) The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans. Nat Genet 45:262-8
O'Toole, Eileen T; Giddings Jr, Thomas H; Porter, Mary E et al. (2012) Computer-assisted image analysis of human cilia and Chlamydomonas flagella reveals both similarities and differences in axoneme structure. Cytoskeleton (Hoboken) 69:577-90

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