| Description |
The Endoplasmic Reticulum (ER) is a cellular organelle responsible for the synthesis and folding of secretory proteins. When protein import into the ER exceeds the its protein folding capacity, misfolded proteins accumulate and can potentially become toxic to the cell. This situation, termed ER stress, activates the Unfolded Protein Response (UPR) to restore the balance between protein folding and protein import. One of the main pathways of the UPR is initiated by Ire1, a ribonuclease in the ER membrane that catalyzes the degradation of ER-associated mRNA. This degradation decreases the workload of the organelle since mRNA attaching to the ER precedes protein import. A major mRNA target of Ire1 in mammalian cells encodes Blos1, a subunit of BORC which is a protein complex used to transport lysosomes along microtubules (Pu et al., 2015). Past experiments have shown that persistent ER stress leads to lysosomes gathering at one side of the nucleus of a cell. Without stress, lysosomes are typically evenly dispersed throughout the cytoplasm. How or why the lysosomes cluster at the nucleus during ER stress is not well understood. This thesis is aimed to display the individual research contributed to the paper "Degradation of Blos1 mRNA by IRE1 repositions lysosomes and protects cells from stress" published in the Journal of Cell Biology (Bae et al., 2019). |
