Cytosolic quality control of secretory and membrane proteins


Funding source

Swedish Research Council - Vetenskapsrådet (VR)


Project Details

Start date: 01/01/2012
End date: 31/12/2012
Funding: 4000000 SEK


Description

A substantial proportion of the genome encodes membrane proteins that are delivered to the endoplasmic reticulum by specific targeting pathways. Membrane proteins that fail targeting must be degraded to avoid aggregation and disruption of cytosolic homeostasis. The mechanisms of mislocalized protein (MLP) degradation are not yet fully known. The overall goal of this proposal is to develop a molecular understanding of how MLP are handled by the cell and of the physiologic importance of quality control of mislocalized secretory and membrane protein. The studies proposed in this application aim at understanding the cytosolic quality control for mislocalized secretory and membrane proteins that are not efficiently recognized and targeted to native compartments. In the first project I will explore the role of the newly identified Bag6 complex in recognizing and degrading MLP; in the second project I will identify the machinery and reconstitute the mechanism of mislocalized proteins degradation; finally, in the third project I will study the initial steps governing biogenesis of pre-proinsulin mutants that cause diabetes. I will test the newly discovered protein quality control-degradation machinery in degradation of mislocalized proinsulin. This study will provide new important insights into protein quality control mechanisms and will help to understand how cells can ensure that dangerous hydrophobic proteins will not accumulate in the cytosol.

Last updated on 2017-31-03 at 12:55