Cells have elaborated a complex strategy to maintain protein homeostasis under physiological as well as stress conditions with the aim to ensure the smooth functioning of vital processes and producing healthy offspring. Impairment of one of the most important processes in living cells, translation, might have serious consequences including various brain disorders in humans. Here, we describe a variant of the translation initiation factor eIF3a, Rpg1-3, mutated in its PCI domain that displays an attenuated translation efficiency and formation of reversible assemblies at physiological growth conditions. Rpg1-3-GFP assemblies are not sequestered within mother cells only as usual for misfolded-protein aggregates and are freely transmitted from the mother cell into the bud although they are of non-amyloid nature. Their bud-directed transmission and the active movement within the cell area depend on the intact actin cytoskeleton and the related molecular motor Myo2. Mutations in the Rpg1-3 protein render not only eIF3a but, more importantly, also the eIF3 core complex prone to aggregation that is potentiated by the limited availability of Hsp70 and Hsp40 chaperones. Our results open the way to understand mechanisms yeast cells employ to cope with malfunction and aggregation of essential proteins and their complexes.

• MeSH
• eukaryotický iniciační faktor 3 genetika   MeSH
• lidé MeSH
• mikrofilamenta genetika   MeSH
• mitochondrie MeSH
• mutace MeSH
• myosin typu V genetika   MeSH
• proteinové agregáty genetika   MeSH
• proteiny tepelného šoku HSP40 genetika   MeSH
• proteiny tepelného šoku HSP70 genetika   MeSH
• Saccharomyces cerevisiae - proteiny genetika   MeSH
• Saccharomyces cerevisiae genetika   růst a vývoj   MeSH
• těžké řetězce myosinu genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Actin networks drive many essential cellular processes, including cell migration, cytokinesis and tissue morphogenesis. However, how cells organize and regulate dynamic actin networks that consist of long, unbranched actin filaments is only poorly understood. This study in mouse oocytes reveals that cells can use vesicles as adaptable, motorized network nodes to regulate the dynamics and density of intracellular actin networks. In particular, Rab11a-positive vesicles drive the network dynamics in a myosin-Vb-dependent manner, and modulate the network density by sequestering and clustering the network's actin nucleators. We also report a simple way by which networks of different densities can be generated, namely by adjusting the number and volume of vesicles in the cell. This vesicle-based mechanism of actin network modulation is essential for asymmetric positioning of the meiotic spindle in mouse oocytes, a vital step in the development of a fertilizable egg in mammals.

• MeSH
• aktiny * metabolismus   MeSH
• aparát dělícího vřeténka * metabolismus   MeSH
• biologické modely MeSH
• cytoplazmatické vezikuly * metabolismus   MeSH
• fluorescenční protilátková technika MeSH
• konfokální mikroskopie MeSH
• kultivované buňky MeSH
• myosin typu V metabolismus   MeSH
• myši MeSH
• oocyty cytologie   metabolismus   MeSH
• rab proteiny vázající GTP * metabolismus   MeSH
• těžké řetězce myosinu metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH