Lisa Swanton, Ph.D. - "Quality control of transmembrane domains within the secretory pathway"
Apr 12, 2017
from 12:00 PM to 01:30 PM
|Where||tigem Auditorium "Vesuvius"|
|Contact Name||Roman Polishchuk|
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Cells are constantly threatened by the production of misfolded and damaged proteins, the accumulation of which can be catastrophic. Therefore, proteins that fail to fold correctly or become damaged must be efficiently identified and eliminated. This is achieved by quality control systems which detect specific features of misfolded proteins and target them for degradation by the proteasome or in lysosomes. Around 20% of the human proteome is made up of integral membrane proteins, which have one or more hydrophobic transmembrane domains that anchor the protein into the lipid bilayer. The biosynthesis of membrane proteins is a complex process and many human diseases are linked to the misfolding of membrane proteins. Therefore, there is great interest in understanding the quality control pathways that identify and remove misfolded membrane proteins in order to maintain cellular and organismal integrity. In contrast to the well-studied quality control systems that scrutinise folding of protein domains in the cytoplasm and endoplasmic reticulum lumen, little is known about the how folding and assembly of transmembrane domains within the lipid bilayer is monitored. In this talk, I will describe our recent work examining where and how non-native transmembrane domains are detected within mammalian cells. Our results point to the existence of multiple transmembrane domain-based quality control checkpoints, including a novel mechanism that detects and rapidly removes proteins containing non-native transmembrane domains from the plasma membrane.