Cells are equipped with a diverse network of signaling and regulatory proteins that function as cell cycle regulators and checkpoint proteins to ensure the proper progression of cell division. A key regulator of cell division is polo-like kinase 1 (PLK1), a member of the serine/threonine kinase family that plays an important role in regulating the mitotic and meiotic cell cycle. The phosphorylation of specific substrates mediated by PLK1 controls nuclear envelope breakdown (NEBD), centrosome maturation, proper spindle assembly, chromosome segregation, and cytokinesis. In mammalian oogenesis, PLK1 is essential for resuming meiosis before ovulation and for establishing the meiotic spindle. Among other potential roles, PLK1 regulates the localized translation of spindle-enriched mRNAs by phosphorylating and thereby inhibiting the translational repressor 4E-BP1, a downstream target of the mTOR (mammalian target of rapamycin) pathway. In this review, we summarize the functions of PLK1 in mitosis, meiosis, and cytokinesis and focus on the role of PLK1 in regulating mRNA translation. However, knowledge of the role of PLK1 in the regulation of meiosis remains limited.

• Klíčová slova
• PLK1, mRNA translation, meiosis, mitosis, oocytes, polo-like kinase 1, spindle,
• MeSH
• lidé MeSH
• meióza MeSH
• mitóza MeSH
• polo-like kinasa 1 MeSH
• protein-serin-threoninkinasy * metabolismus   MeSH
• proteiny buněčného cyklu * metabolismus   MeSH
• protoonkogenní proteiny metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• protein-serin-threoninkinasy * MeSH
• proteiny buněčného cyklu * MeSH
• protoonkogenní proteiny MeSH

The tight correlation between mRNA distribution and subsequent protein localization and function indicate a major role for mRNA localization within the cell. RNA localization, followed by local translation, presents a mechanism for spatial and temporal gene expression regulation utilized by various cell types. However, little is known about mRNA localization and translation in the mammalian oocyte and early embryo. Importantly, fully-grown oocyte becomes transcriptionally inactive and only utilizes transcripts previously synthesized and stored during earlier development. We discovered an abundant RNA population in the oocyte and early embryo nucleus together with RNA binding proteins. We also characterized specific ribosomal proteins, which contribute to translation in the oocyte and embryo. By applying selected markers to mouse and human oocytes, we found that there might be a similar mechanism of RNA metabolism in both species. In conclusion, we visualized the localization of RNAs and translation machinery in the oocyte, that could shed light on this terra incognita of these unique cell types in mouse and human.

• MeSH
• embryo savčí metabolismus   ultrastruktura   MeSH
• kultivované buňky MeSH
• lidé MeSH
• messenger RNA analýza   genetika   MeSH
• myši MeSH
• oocyty metabolismus   ultrastruktura   MeSH
• proteiny vázající RNA analýza   genetika   MeSH
• proteosyntéza * MeSH
• transkriptom MeSH
• vývojová regulace genové exprese * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• messenger RNA MeSH
• proteiny vázající RNA MeSH

The adenylate cyclase toxin (CyaA) of the whooping cough agent Bordetella pertussis subverts immune functions of host myeloid cells expressing the αMβ2 integrin (CD11b/CD18, CR3 or Mac-1). CyaA delivers into cytosol of cells an extremely catalytically active adenylyl cyclase enzyme, which disrupts the innate and adaptive immune functions of phagocytes through unregulated production of the key signaling molecule cAMP. We have used phosphoproteomics to analyze cAMP signaling of CyaA in murine bone marrow-derived dendritic cells. CyaA action resulted in alterations of phosphorylation state of a number of proteins that regulate actin cytoskeleton homeostasis, including Mena, Talin-1 and VASP. CyaA action repressed mTOR signaling through activation of mTORC1 inhibitors TSC2 and PRAS40 and altered phosphorylation of multiple chromatin remodelers, including the class II histone deacetylase HDAC5. CyaA toxin action further elicited inhibitory phosphorylation of SIK family kinases involved in modulation of immune response and provoked dephosphorylation of the transcriptional coactivator CRTC3, indicating that CyaA-promoted nuclear translocation of CRTC3 may account for CyaA-induced IL-10 production. These findings document the complexity of subversive physiological manipulation of myeloid phagocytes by the CyaA toxin, serving in immune evasion of the pertussis agent.

• MeSH
• AMP cyklický metabolismus   MeSH
• Bordetella pertussis metabolismus   MeSH
• cytoskeletální proteiny metabolismus   MeSH
• dendritické buňky metabolismus   MeSH
• fosfoprotein stimulovaný vazodilatátorem MeSH
• fosfoproteiny metabolismus   MeSH
• histondeacetylasy metabolismus   MeSH
• mikrofilamentové proteiny metabolismus   MeSH
• molekuly buněčné adheze metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• pertuse mikrobiologie   MeSH
• signální transdukce fyziologie   MeSH
• talin metabolismus   MeSH
• transkripční faktory metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• AMP cyklický MeSH
• CRTC3 protein, mouse MeSH Prohlížeč
• cytoskeletální proteiny MeSH
• Enah protein, mouse MeSH Prohlížeč
• fosfoprotein stimulovaný vazodilatátorem MeSH
• fosfoproteiny MeSH
• Hdac5 protein, mouse MeSH Prohlížeč
• histondeacetylasy MeSH
• mikrofilamentové proteiny MeSH
• molekuly buněčné adheze MeSH
• talin MeSH
• Tln1 protein, mouse MeSH Prohlížeč
• transkripční faktory MeSH

Bordetellae, pathogenic to mammals, produce an immunomodulatory adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) that enables them to overcome the innate immune defense of the host. CyaA subverts host phagocytic cells by an orchestrated action of its functional domains, where an extremely catalytically active adenylyl cyclase enzyme is delivered into phagocyte cytosol by a pore-forming repeat-in-toxin (RTX) cytolysin moiety. By targeting sentinel cells expressing the complement receptor 3, known as the CD11b/CD18 (αMβ₂) integrin, CyaA compromises the bactericidal functions of host phagocytes and supports infection of host airways by Bordetellae. Here, we review the state of knowledge on structural and functional aspects of CyaA toxin action, placing particular emphasis on signaling mechanisms by which the toxin-produced 3',5'-cyclic adenosine monophosphate (cAMP) subverts the physiology of phagocytic cells.

• Klíčová slova
• Bordetella, CD11b/CD18, adenylate cyclase toxin, cAMP, cell signaling, complement receptor 3, innate immunity, membrane pores, repeats-in-toxin, β2 integrins,
• MeSH
• adenylátcyklasový toxin chemie   MeSH
• alveolární makrofágy cytologie   MeSH
• AMP cyklický chemie   MeSH
• Bordetella pertussis MeSH
• dendritické buňky cytologie   MeSH
• fagocyty chemie   MeSH
• kinasa Syk MeSH
• lidé MeSH
• makrofágový antigen 1 MeSH
• neutrofily cytologie   MeSH
• proteinové domény MeSH
• signální transdukce * MeSH
• terciární struktura proteinů MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• adenylátcyklasový toxin MeSH
• AMP cyklický MeSH
• kinasa Syk MeSH
• makrofágový antigen 1 MeSH
• SYK protein, human MeSH Prohlížeč

Fully grown mammalian oocytes utilize transcripts synthetized and stored during earlier development. RNA localization followed by a local translation is a mechanism responsible for the regulation of spatial and temporal gene expression. Here we show that the mouse oocyte contains 3 forms of cap-dependent translational repressor expressed on the mRNA level: 4E-BP1, 4E-BP2 and 4E-BP3. However, only 4E-BP1 is present as a protein in oocytes, it becomes inactivated by phosphorylation after nuclear envelope breakdown and as such it promotes cap-dependent translation after NEBD. Phosphorylation of 4E-BP1 can be seen in the oocytes after resumption of meiosis but it is not detected in the surrounding cumulus cells, indicating that 4E-BP1 promotes translation at a specific cell cycle stage. Our immunofluorescence analyses of 4E-BP1 in oocytes during meiosis I showed an even localization of global 4E-BP1, as well as of its 4E-BP1 (Thr37/46) phosphorylated form. On the other hand, 4E-BP1 phosphorylated on Ser65 is localized at the spindle poles, and 4E-BP1 phosphorylated on Thr70 localizes on the spindle. We further show that the main positive regulators of 4E-BP1 phosphorylation after NEBD are mTOR and CDK1 kinases, but not PLK1 kinase. CDK1 exerts its activity toward 4E-BP1 phosphorylation via phosphorylation and activation of mTOR. Moreover, both CDK1 and phosphorylated mTOR co-localize with 4E-BP1 phosphorylated on Thr70 on the spindle at the onset of meiotic resumption. Expression of the dominant negative 4E-BP1 mutant adversely affects translation and results in spindle abnormality. Taken together, our results show that the phosphorylation of 4E-BP1 promotes translation at the onset of meiosis to support the spindle assembly and suggest an important role of CDK1 and mTOR kinases in this process. We also show that the mTOR regulatory pathway is present in human oocytes and is likely to function in a similar way as in mouse oocytes.

• Klíčová slova
• 4E-BP1, CDK1, cumulus cells, kinase, mRNA, mTOR, meiosis, oocyte, spindle, translation,
• MeSH
• adaptorové proteiny signální transdukční MeSH
• aparát dělícího vřeténka genetika   MeSH
• buněčný cyklus genetika   MeSH
• eukaryotické iniciační faktory MeSH
• fosfoproteiny genetika   metabolismus   MeSH
• fosforylace MeSH
• lidé MeSH
• myši MeSH
• oocyty růst a vývoj   metabolismus   MeSH
• proteinkinasa CDC2 genetika   MeSH
• proteiny buněčného cyklu MeSH
• proteosyntéza MeSH
• TOR serin-threoninkinasy genetika   MeSH
• transportní proteiny genetika   metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• Eif4ebp1 protein, mouse MeSH Prohlížeč
• eukaryotické iniciační faktory MeSH
• fosfoproteiny MeSH
• mTOR protein, mouse MeSH Prohlížeč
• proteinkinasa CDC2 MeSH
• proteiny buněčného cyklu MeSH
• TOR serin-threoninkinasy MeSH
• transportní proteiny MeSH

The fully grown mammalian oocyte is transcriptionally quiescent and utilizes only transcripts synthesized and stored during early development. However, we find that an abundant RNA population is retained in the oocyte nucleus and contains specific mRNAs important for meiotic progression. Here we show that during the first meiotic division, shortly after nuclear envelope breakdown, translational hotspots develop in the chromosomal area and in a region that was previously surrounded the nucleus. These distinct translational hotspots are separated by endoplasmic reticulum and Lamin, and disappear following polar body extrusion. Chromosomal translational hotspots are controlled by the activity of the mTOR-eIF4F pathway. Here we reveal a mechanism that-following the resumption of meiosis-controls the temporal and spatial translation of a specific set of transcripts required for normal spindle assembly, chromosome alignment and segregation.

• MeSH
• časové faktory MeSH
• down regulace MeSH
• eukaryotický iniciační faktor 4F metabolismus   MeSH
• fertilizace MeSH
• jaderný obal metabolismus   MeSH
• lidé MeSH
• meióza MeSH
• messenger RNA genetika   metabolismus   MeSH
• myši MeSH
• nestabilita genomu MeSH
• oocyty metabolismus   MeSH
• proteosyntéza * MeSH
• RNA čepičky metabolismus   MeSH
• savčí chromozomy metabolismus   MeSH
• savci metabolismus   MeSH
• signální transdukce * MeSH
• TOR serin-threoninkinasy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• eukaryotický iniciační faktor 4F MeSH
• messenger RNA MeSH
• RNA čepičky MeSH
• TOR serin-threoninkinasy MeSH