|
|
Regulatory mechanisms of centrosomal microtubule nucleation
Klebanovych, Anastasiya ; Dráber, Pavel (advisor) ; Hašek, Jiří (referee) ; Vomastek, Tomáš (referee)
The spatio-temporal organization and dynamic behavior of microtubules accurately react to cellular needs during intracellular transport, signal transduction, growth, division, and differentiation. The cell generates centrosomal microtubules de novo with the help of γ-tubulin complexes (γTuRCs). The post-translational modifications fine-tune microtubule nucleation by targeting the proteins, interacting with γTuRCs. However, the exact signaling pathways, regulating centrosomal microtubule nucleation, remain mostly unknown. In the presented thesis, we functionally characterized protein tyrosine phosphatase SHP-1 and E3 UFM-protein ligase 1 (UFL1) with its interacting protein CDK5RAP3 (C53) in the regulation of centrosomal microtubule nucleation. We also elucidated the role of actin regulatory protein profilin 1 in this process. We found that SHP-1 formed complexes with γTuRC proteins and negatively regulated microtubule nucleation by modulating the amount of γ-tubulin/γTuRC at the centrosomes in bone marrow-derived mast cells (BMMCs). We suggested a novel mechanism with centrosomal tyrosine-phosphorylated Syk kinase, targeted by SHP-1 during Ag-induced BMMCs activation, regulating microtubules. We showed for the first time that UFL1/C53 protein complex is involved in the regulation of microtubule...
|
|
|
Sperm centrioles and their role in reproduction
Vlčková, Monika ; Frolíková, Michaela (advisor) ; Liška, František (referee)
Centrioles are evolutionarily conserved protein structures composed of microtubules. In somatic cells, centrioles serve as the basal body of cilia and flagella and allow the assembly of pericentriolar material, thereby creating the centrosome. Without centrosome, animal cells are not capable of nuclear division. Centrioles do not arise de novo and their formation always requires the presence of a preexisting centriole. Since there are no centrioles in the egg at the time of fertilization, unlike spermatozoa, sperm is the carrier of centrioles and therefore all of the centrioles of the emerging organism are of paternal origin. There are two centrioles in the sperm - a cylindrical shape proximal and a distal one, which is perpendicular to the proximal. The sperm centrioles are the basis for the formation of the sperm flagellum and after fertilization form the mitotic spindle of the zygote, necessary for equal DNA and cell distribution. It follows from the above that the presence of centrioles in sperm is essential in mammals and defects in their structure may lead to male sterility or embryo development disorders. However, sperm centrioles differ from somatic centrioles in their structure and behavior and understanding these differences is one of the important tasks of reproductive biology.
|
|
|
Role of Polo-like kinases in the cell cycle and DNA damage response
Kudláčková, Radmila ; Macůrek, Libor (advisor) ; Šolc, Petr (referee)
Within the process of cell division, genetic material must be equally distributed between the two daughter cells. In the next phase, the missing portion of the genome must be synthesized. The entire cycle is regulated by cyclin-dependent kinases (Cdks) in cooperation with cyclins. If the DNA is damaged during the cell cycle, signaling pathways of checkpoints supress cycle progression and enforce the cell cycle arrest until the damage is repaired. Malfunction of the checkpoints results in tumorigenesis. Polo-like kinases (Plks) are, much like Cdks, important regulators of the cell cycle. Plks play significant role mainly in the mitosis and also in a response to the DNA damage. This thesis is focused on human homologues, nevertheless conservation of homologues among organisms is considerable, thus presented findings are of general relevance. Human cells express five proteins from the family of Polo-like kinases, from which Plk1 corresponds to Polo-like kinases of lower eukaryotes. Knowledge on the remaining four kinases is still on the rise.
|
|
|
Plant microtubule-organizing centers
Škrdlová, Iveta ; Schwarzerová, Kateřina (advisor) ; Libusová, Lenka (referee)
In eukaryotic cells, microtubules are nucleated and organized by protein structures called microtubule- organizing centers. There is a great diversity in structure and morphology of these structures in eukaryotic organisms. Animal centrosome, yeast spindle pole body and basal bodies of flagellar apparatus are the best known types of so called focused microtubule-organizing centers, where microtubules are nucleated from one or two concrete sites in the cell. These focused microtubule- organizing centers are replaced by diffuse centers in higher plant cells, which means that microtubules are nucleated from dispersed nucleation sites. Focused centers are rarely found in land plant cells. These focused centers comprise bicentrioles and blepharoplasts, which give rise to the locomotory apparatus of motile spermatozoid of bryophytes, pteridophytes, cycads and Ginkgo. Another types of focused microtubule-organizing centers in bryophytes are polar organizers, and the nuclear and the plastid envelopes in mitotic and meiotic cells. Powered by TCPDF (www.tcpdf.org)
|
|
| |
guest ::
