The long-term objective of this proposal is the understanding of the molecular mechanism that creates bending and waveforms of cilia and flagella. To reach this objective studies will be performed to describe the position and function of the inner dynein arms along and across the axonemes of Chlamydomonas flagella. The inner dynein arms produce shear forces at different points along outer doublet microtubules and, therefore, create and maintain axonemal bends. Other axonemal substructures, such as the """"""""dynein regulatory complex"""""""" (drc) and the radial spokes modify the waveforms of the axonemes. In contrast, motors, such as the outer dynein arms, affect the beat frequency of the axonemes. The long term objective will be approached through the following specific aims: 1) identify the position within the axoneme of specific light, intermediate and heavy chains of inner dynein arms. 2) identify the function of specific inner dynein arms in the initiation and propagation of axonemal waveforms. 3) describe the interactions occurring in the ensemble of inner dynein arms, radial spokes and drc at the molecular level. 4) determine whether axoneme assembly depends on active transport of specific inner dynein arm subunits. A model of the inner dynein arm organization along and across the axoneme will be tested by these experimental approaches. The following hypotheses also will be tested: 1) each form of inner dynein arm affects a particular characteristic of axonemal waveforms, 2) the protein centrin provides a calcium-dependent regulation of inner dynein arm activity, 3) proximal inner dynein arm subunits are transported actively to their final destination. The axonemes of Chlamydomonas flagella are an excellent model system for studies of cilia and flagella of complex organisms. They are functionally and morphologically similar to axonemes from a variety of sources. Furthermore, they can be analyzed by genetics. Cilia or flagella are appended to various cell types in the human body such as: epithelial cells lining the respiratory tracts, the oviduct cells, sperm cells and the ependymal cells in the spinal cord. Axonemal dysfunctions in humans may cause respiratory ailments or sterility or the """"""""Kartagener's syndrome"""""""" or hydrocephalus.
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