An efficient delivery of DAMPs on the cell surface by the unconventional secretion pathway

Damage-associated molecular patterns (DAMPs) are signals released from dying cells evoking the immune system response in several inflammatory disorders. In normal situations, many of DAMPs are nuclear or cytosolic proteins with defined intracellular function, but they could be found on the cell surface following tissue injury. The biological function of the translocated DAMPs is still not well known and an efficient delivery of these molecules on the cell surface is required to clarify their biological effects. In this study, we demonstrated that an unclassical secretory signal peptide, N-terminal 18 amino acids of HASPB (HASPB-N18), could efficiently deliver Hsp60, Hsp70, and HMGB1 on the cell surface. Furthermore, the delivery of these molecules on the cell surface by HASPB-N18 is not limited to a special cell line because several cell lines could use this delivery signal to deliver these molecules on the cell surface. Moreover, we demonstrated that Hsp60 on the cell surface delivered by HASPB-N18 could be recognized by a soluble form of LOX-1, which implies that DAMPs on the cell surface delivered by HASPB-N18 have a proper conformation during transport. Therefore, delivery of DAMPs by HASPB-N18 is a reliable model to further understand the biological significance of DAMPs on the cell surface.

Research highlights
► Hsp60 transported to cell surface through the classical secretory pathway was modified with N-glycosylation.
► HSAPB-N18 could efficiently deliver Hsp60 to the cell surface via the unconventional secretory pathway.
► Cell surface Hsp60 delivered by HASPB-N18 has a proper conformation.
► HASPB-N18 is an efficient delivery signal for other DAMP molecules such as Hsp70 and HMGB1.