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The role of Sas-4 in ciliogenesis and centriole biogenesis in Drosophila

Wang, Yongheng
http://orcid.org/0000-0002-7675-2327
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1461074141

Abstract Details

2016, Master of Science, University of Toledo, Biology (Cell-Molecular Biology).
The centrosome is an organelle essential for microtubule nucleation, cell division and cilia formation. A centrosome consists of a pair of centrioles surrounded by pericentriolar materials (PCM). Sas-4 is a PCM protein containing 901 amino acids. Replacing two adjacent arginine residues (R114 and R115) of Sas-4 with two glutamic acids resulted in paralysis of the Drosophila carrying these mutations. We found the paralysis was due to malfunctioned mechanosensation, a condition when the sensory neurons could not generate current after touch. Furthermore, we found the faulty mechanosensation was caused by the absence of cilia, which are hair-like projections enriched with ion-channels and receptors on the surface of cells. Our data suggest that Sas-4 plays a role in cilia formation; a process is also termed ciliogenesis. However, it is not clear how Sas-4 regulates ciliogenesis. To form a cilium, a centrosome needs to migrate from the center of a cell to the plasma membrane and undergo some modifications, which include the removal of protein CP110 from the centrosome and the recruitment of transition zone (TZ) proteins and intraflagellar transport (IFT) proteins to the centrosome. We found that a transition zone protein Chibby (CBY) was recruited to the centrosome in the above-mentioned transgenic Drosophila, suggesting that Sas-4 regulates ciliogenesis by a mechanism independent of the recruitment of TZ proteins. Further investigations on the recruitment of IFT proteins to the TZ in the transgenic Drosophila will help us determine the role of Sas-4 in ciliogenesis. Another objective of our project is to study the role of Sas-4 in centriole formation. A centriole contains 9 fold symmetry microtubules. ¿-Tubulin large ring complexes (¿-TuRC) are needed to nucleate the centriolar microtubules. It is not clear how ¿-TuRC is recruited to the procentriole. Procentriole refers to a centriole in a stage of early development. We have shown that Sas-4 could bind ¿ TuRC; and that Sas-4 serves as a scaffold and tethers PCM protein in a centrosome. Therefore, we hypothesize that Sas-4 is essential for the recruitment of ¿-TuRC to the procentriole and disrupting the interaction between Sas-4 and ¿-TuRC will prevent centriole formation. We found the amino acids 25 to 75 of Sas-4 are essential for binding ¿-TuRC. Further investigation on the phenotype of the transgenic Drosophila lacking the ¿-TuRC-binding region of Sas-4 will help us understand the role of Sas-4 in centriole biogenesis.
Tomer Avidor-Reiss (Committee Chair)
Qian Chen (Committee Member)
Guofa Liu (Committee Member)
Song-Tao Liu (Committee Member)
45 p.
Biology
Sas-4, ciliogenesis, centrosome biogenesis

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Citations

  • Wang, Y. (2016). The role of Sas-4 in ciliogenesis and centriole biogenesis in Drosophila [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1461074141

    APA Style (7th edition)

  • Wang, Yongheng. The role of Sas-4 in ciliogenesis and centriole biogenesis in Drosophila. 2016. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1461074141.

    MLA Style (8th edition)

  • Wang, Yongheng. "The role of Sas-4 in ciliogenesis and centriole biogenesis in Drosophila." Master's thesis, University of Toledo, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1461074141

    Chicago Manual of Style (17th edition)

toledo1461074141
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This open access ETD is published by University of Toledo and OhioLINK.