Jingshi Shen - Genome-scale dissection of mammalian membrane...
Channel: Institut des Hautes Études Scientifiques (IHÉS)
Date: 2018-03-26

Genome-scale dissection of mammalian membrane trafficking – new players and unexpected mechanisms

Cargo proteins moving between organelles are transported by membrane-enclosed vesicles. The core engines mediating vesicle trafficking are now well established. However, we are only beginning to understand the regulatory networks superimposed upon the core engines to adjust the rate and direction  of  membrane  transport  according  to  physiological  demands.  The  advent  of  the revolutionary  CRISPR-Cas9  genome  editing  system  enabled  us  to  systematically  identify  new components of the regulatory networks. We developed new screening platforms and performed unbiased genome-wide CRISPR genetic screens to dissect the exocytosis and endocytosis of cell surface  transporters,  fundamental  processes  in  cell  physiology.  Our  screens  identified  known regulators but most of the hits were not previously known to regulate the pathways. I will focus on 
the unexpected mechanisms of RABIF/MSS4 in exocytosis and AAGAB in endocytosis. I will also discuss how the principles uncovered in our studies shed light on vesicle trafficking in general.