MOLECULAR INTERACTIONS IN MOVING AXONEMES

这项建议的长期目标是理解 产生纤毛和纤毛波形的分子机制 鞭毛。为了达到这一目标，将进行研究以描述 内侧动力蛋白臂沿和横跨关节的位置和功能 鞭毛衣藻的轴丝。内部动力蛋白臂产生剪切力 沿外部双线微管的不同点的力， 因此，创建并保持轴突弯曲。其他轴突 亚结构，如“动力蛋白调节复合体”(DRC)和 径向辐条改变了轴突的波形。相比之下，马达， 如外动力蛋白臂，影响轴突的搏动频率。 将通过以下具体措施实现长期目标 目标： 1)识别特定光的轴丝内的位置， 内部动力蛋白手臂的中链和重链。 2)确定特定的内动力蛋白臂在启动过程中的功能 以及轴突波形的传播。 3)描述内部动力系统中发生的相互作用 分子水平上的手臂、径向辐条和DRC。 4)确定轴丝组装是否依赖于主动转运 特定的内部动力蛋白臂亚单位。 沿轴丝和跨轴丝的内动力蛋白臂组织模型 将通过这些实验方法进行测试。以下假设 还将测试：1)每种形式的内部动力蛋白手臂都会影响一个特定的 轴突波形的特征，2)蛋白中心素提供 内动力蛋白臂活动的钙依赖性调节，3)近端 内部动力蛋白臂亚单位被积极地运输到它们的最终 目的地。 鞭毛衣藻的轴丝是一种很好的模式系统 复合体的纤毛和鞭毛的研究。它们在功能上 在形态上与来自不同来源的轴丝相似。 此外，它们还可以通过遗传学进行分析。 纤毛或鞭毛附着于人体内的各种细胞类型。 如：呼吸道、输卵管衬里的上皮细胞 脊髓中的细胞、精子细胞和室管膜细胞。轴向 人类的功能障碍可能会导致呼吸道疾病或不孕不育或 “Karagener综合征”或脑积水。

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.