Translation stress positively regulates MscL-dependent excretion of cytoplasmic proteins

The apparent mislocalization or excretion of cytoplasmic proteins is a commonly observed phenomenon in both bacteria and eukaryotes. However, reports on the mechanistic basis and the cellular function of this so called “non-classical protein secretion” are limited. Here we report that protein over-expression in recombinant cells and antibiotic-induced translation stress in wild-type E.
coli cells, both lead to excretion of cytoplasmic protein (ECP). Condition-specific metabolomic and proteomic analyses combined with genetic knockouts, indicate a role of both the large mechanosensitive channel (MscL) and the alternative ribosome-rescue factor A (ArfA) in ECP. Collectively, the findings indicate that the MscL-dependent protein excretion is positively regulated in response to both osmotic and arfA-mediated translational stress.