Objective
The nucleus, surrounded by the nuclear envelope (NE), houses genetic material, and nuclear pore complexes (NPCs) mediate the selective passage of molecules between the nucleus and the cytoplasm. NPCs are critical for cellular functions such as protein synthesis and cell division. Dysfunction of NPCs is associated with ageing and disease, highlighting the importance of quality control mechanisms such as NPC degradation. However, the pathways that control NPC degradation remain largely uncharacterized.
A recent study in yeast revealed for the first time a selective autophagy pathway responsible for the degradation of fully assembled NPCs embedded in the NE. NE-derived NPC-containing vesicles are engulfed by an autophagosome through the initial binding of Atg8 to the cytoplasmic-facing Nup159. Although Nup159 is present in all NPCs, NPC degradation occurs rarely under normal conditions and is only upregulated under stress conditions such as starvation, indicating a tightly regulated process.
This research, using Saccharomyces cerevisiae as a model, aims to uncover the machinery and triggers that regulate autophagic NPC degradation through two main objectives. First, to identify the machinery required for the formation of NPC-containing vesicles, using a powerful combination of genome-wide screening and structural insights from cryo-electron tomography. Second, to determine the mechanisms that trigger the formation of NPC-containing vesicles, focusing on two likely triggers: NPC clustering and nuclear content.
The results of this study will redefine our knowledge of NPC quality control and the autophagic degradation pathway for NPCs. The knowledge gained from processes in yeast can potentially be extended to human cell biology, where NPC integrity is crucial in ageing and disease.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
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Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
80539 Munchen
Germany