title: An efficient delivery of DAMPs on the cell surface by the unconventional secretion pathway.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical Collage, Fudan University, Shanghai 200032, PR China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhu
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ruan
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Min
authors.forename: Jianhui
authors.initials: J
authors.lastname: Xie
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism*; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism*; D018834:Chaperonin 60 / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D021381:Protein Transport; D015800:Protozoan Proteins / Q000378:metabolism*
chemical_list: D000953:Antigens, Protozoan; D018834:Chaperonin 60; C401884:HASPB protein, Leishmania; D015800:Protozoan Proteins