Equal segregation of chromosomes during mitosis ensures euploidy of daughter cells. Defects in this process may result in an imbalance in the chromosomal composition and cellular transformation. Proteolytic and non-proteolytic ubiquitylation pathways ensure directionality and fidelity of mitotic progression but specific mitotic functions of deubiquitylating enzymes (DUBs) remain less studied. Here we describe the role of the DUB ubiquitin carboxyl-terminal hydrolase isozyme L3 (UCHL3) in the regulation of chromosome bi-orientation and segregation during mitosis. Downregulation or inhibition of UCHL3 leads to chromosome alignment defects during metaphase. Frequent segregation errors during anaphase are also observed upon inactivation of UCHL3. Mechanistically, UCHL3 interacts with and deubiquitylates Aurora B, the catalytic subunit of chromosome passenger complex (CPC), known to be critically involved in the regulation of chromosome alignment and segregation. UCHL3 does not regulate protein levels of Aurora B or the binding of Aurora B to other CPC subunits. Instead, UCHL3 promotes localization of Aurora B to kinetochores, suggesting its role in the error correction mechanism monitoring bi-orientation of chromosomes during metaphase. Thus, UCHL3 contributes to the regulation of faithful genome segregation and maintenance of euploidy in human cells.
- MeSH
- aurora kinasa B fyziologie MeSH
- HeLa buňky MeSH
- lidé MeSH
- mitóza * MeSH
- segregace chromozomů * MeSH
- thiolesterasa ubikvitinu fyziologie MeSH
- ubikvitinace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Regulation of axon guidance and pruning of inappropriate synapses by class 3 semaphorins are key to the development of neural circuits. Collapsin response mediator protein 2 (CRMP2) has been shown to regulate axon guidance by mediating semaphorin 3A (Sema3A) signaling; however, nothing is known about its role in synapse pruning. Here, using newly generated crmp2-/- mice we demonstrate that CRMP2 has a moderate effect on Sema3A-dependent axon guidance in vivo, and its deficiency leads to a mild defect in axon guidance in peripheral nerves and the corpus callosum. Surprisingly, crmp2-/- mice display prominent defects in stereotyped axon pruning in hippocampus and visual cortex and altered dendritic spine remodeling, which is consistent with impaired Sema3F signaling and with models of autism spectrum disorder (ASD). We demonstrate that CRMP2 mediates Sema3F signaling in primary neurons and that crmp2-/- mice display ASD-related social behavior changes in the early postnatal period as well as in adults. Together, we demonstrate that CRMP2 mediates Sema3F-dependent synapse pruning and its dysfunction shares histological and behavioral features of ASD.
- MeSH
- dendritické trny MeSH
- membránové proteiny fyziologie MeSH
- mezibuněčné signální peptidy a proteiny genetika MeSH
- myši knockoutované MeSH
- myši MeSH
- neurony MeSH
- neuroplasticita MeSH
- poruchy autistického spektra * MeSH
- proteiny nervové tkáně genetika fyziologie MeSH
- semaforiny * MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cullin-RING ubiquitin ligases (CRLs) represent the largest family of E3 ubiquitin ligases that control most if not all cellular processes. In CUL3-based CRLs, the substrate specificity is conferred by the interaction with one of around 183 existing BTB proteins, implying a broad spectrum of possible ubiquitylation signals and possible direct ubiquitylation substrates. Indeed, CUL3-based E3-ligases can catalyze various proteolytic and non-proteolytic ubiquitin signals regulating many physiological and pathophysiological states. Here, we discuss the recent studies focusing on the non-proteolytic CUL3-based signaling in mammalian cells, which emerge as important pathways during cell division, embryonic development as well as other biological processes. Mechanistically, non-proteolytic ubiquitin signals generated by CUL3 E3-ligases often regulate substrates' interactions with other downstream factors or their subcellular localization. Existing data also demonstrate an interplay with the proteolytic ubiquitylation catalyzed on the same substrates by different E3-ligases or by the same CUL3-BTB CRL3s on different substrates. In future, a deeper understanding of the upstream spatiotemporal regulatory mechanisms will help to dissect this fascinating CUL3 ubiquitin code.
- MeSH
- kulinové proteiny metabolismus MeSH
- lidé MeSH
- proteolýza MeSH
- ubikvitin metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Although the issue of life satisfaction is being discussed in various theoretical disciplines, it has not been defined clearly yet. There are many terms that are close to term life satisfaction, such as happiness, well-being, quality of life etc., these are sometimes used interchangeably. This paper introduces an initial research of life satisfaction of individuals with visual impairment in the Czech Republic. The authors used a standardised Questionnaire of Life Satisfaction by Fahrenberg, Myrtek, Schumacher and Brahler (in Rodná, Rodný, 2001) to find out whether the life satisfaction of individuals with visual impairment differs from statistically given norm.
- MeSH
- dospělí MeSH
- kvalita života * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- průzkumy a dotazníky MeSH
- senioři MeSH
- zrakově postižení * psychologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
Článek je zaměřen na problematiku poranění rukou a replantace prstů. Popisuje průběh transportu pacienta do zdravotnického zařízení, správné ošetření a uložení amputátu a postižené končetiny. Cílem článku je zvýšit informovanost zdravotníků a přispět ke zkvalitnění péče v této oblasti.
The article is focused on the issue of injury to the hands and fingers replantace. It describes the course of transport the patient to a medical facility, proper treatment and the imposition of amputate and affected limbs. The article is to raise awareness of health and contribute to the quality of care in this field.
Skripta
1. vyd. 104 s. : il. ; 29 cm
Cílem publikace je podat studentům speciální pedagogiky ucelený přehled pomůcek užívaných osobami s tělesným, zrakovým a sluchovým postižením.
- MeSH
- hluchota psychologie rehabilitace MeSH
- lidé MeSH
- postižení psychologie rehabilitace výchova MeSH
- slepota psychologie rehabilitace MeSH
- výchova a vzdělávání metody organizace a řízení trendy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- recenze MeSH
